Interferons are a group of signaling proteins produced by the cells of the immune system in horses in response to viral infections and other immune challenges. They are part of the innate immune response and help regulate the activity of the immune system by inhibiting viral replication and modulating the immune response. In horses, interferons are categorized into types I, II, and III, with type I interferons, such as interferon-alpha and interferon-beta, being the most extensively studied. These proteins are integral to the horse's defense mechanisms against viral pathogens and are also explored for their therapeutic potential. This page compiles peer-reviewed research studies and scholarly articles that investigate the production, function, and clinical applications of interferons in equine health.
Galvão A, Valente L, Skarzynski DJ, Szóstek A, Piotrowska-Tomala K, Rebordão MR, Mateus L, Ferreira-Dias G.Regulation of immune-endocrine interactions in the equine endometrium is not fully understood. The aims of the present study were to: (1) investigate the presence of tumour necrosis factor alpha (TNF), interferon gamma (IFNG), Fas ligand (FASLG) and their receptors in the mare endometrium throughout the oestrous cycle; and (2) assess endometrial secretory function (prostaglandins), angiogenic activity and cell viability in response to TNF, oestradiol (E2), progesterone (P4) and oxytocin (OXT). Transcription of TNF and FASLG mRNA increased during the early and late luteal phase (LP), whereas IF...
Sun L, Gong Z, Oberst EJ, Betancourt A, Adams AA, Horohov DW.While born with a limited production, foals' interferon-gamma (IFN-γ) expression increases after birth. The underlying mechanisms remain unknown. DNA methylation is considered to be involved. Therefore, the DNA methylation status of the Ifng promoter in CD4(+) cells from neonatal foal was determined using a methylation-specific PCR (MSP), and its relevance to IFN-γ mRNA expression was estimated. The effect of environment on the DNA methylation was also evaluated by comparing ponies that were kept in a barn versus those on pasture. The DNA in the Ifng promoter was hypermethylated and its deme...
Bauersachs S, Wolf E.Different reproductive strategies evolved in various mammalian groups to achieve recognition, establishment and maintenance of pregnancy. The complexity of these processes is reflected by a high incidence of embryonic loss during this critical period in many mammalian species. Besides studies in mice and humans a number of transcriptome studies of endometrial tissue samples and also of early embryos have been performed during the pre-implantation phase in cattle, swine and horse to identify genes associated with embryo-maternal interaction. Results of these studies are reviewed and compared be...
Tsuchiya T, Hobo S, Endo Y, Narita S, Sakamoto K.To evaluate effects of a single dose of enrofloxacin (5 mg/kg, IV) on body temperature and tracheobronchial neutrophil count in healthy Thoroughbreds premedicated with interferon-α and undergoing long-distance transportation. Methods: 32 healthy Thoroughbreds. Methods: All horses received interferon-α (0.5 U/kg, sublingually, q 24 h) as an immunologic stimulant for 2 days before transportation and on the day of transportation. Horses were randomly assigned to receive enrofloxacin (5 mg/kg, IV, once; enrofloxacin group) or saline (0.9% NaCl) solution (50 mL, IV, once; control group) ≤ 1 hou...
Pawelek KA, Huynh GT, Quinlivan M, Cullinane A, Rong L, Perelson AS.Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and ...
Liu C, Cook FR, Cook SJ, Craigo JK, Even DL, Issel CJ, Montelaro RC, Horohov DW.Distinct from human lentivirus infection, equine infectious anemia virus (EIAV)-infected horses will eventually enter an inapparent carrier state in which virus replication is apparently controlled by adaptive immune responses. Although recrudescence of disease can occur after immune suppression, the actual immune correlate associated with protection has yet to be determined. Therefore, EIAV provides a model for investigating immune-mediated protective mechanisms against lentivirus infection. Here, we have developed a method to monitor EIAV-envelope specific cellular immunity in vivo. An EIA c...
Mignot CC, Pirottin D, Farnir F, de Moffarts B, Molitor C, Lekeux P, Art T.The effects of strenuous exercise and ex vivo stimulation of TLR3 and TLR4 pathways on the expression of six inflammatory genes in equine pulmonary leukocytes were investigated. The genes tested were interferon-beta (IFN-β), interleukin-1-beta (IL-1β), interleukin-6 (IL-6), interferon gamma-induced protein 10 (IP-10), chemokine (c-c motif) ligand 5 (RANTES) and tumor necrosis factor-alpha (TNF-α). We hypothesized that strenuous exercise would modulate basal gene expression on one hand and modulate the response to bacterial lipopolysaccharide (LPS) and to polyinosinic:polycytidylic acid (Pol...
Wattrang E, Palm AK, Wagner B.Synthetic oligodeoxyribonucleotides (ODN) may prove useful immune modulators in equine medicine. It is however important to assess the effects of each specific ODN in the species it is intended to be used in. The present study therefore aimed to evaluate some ODN for induction of cytokine production; i.e. type I interferons (IFN), IFN-γ, tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), and proliferation of equine peripheral blood mononuclear cells (PBMC). A panel of four ODN containing unmethylated cytosine-guanosine sequences (CpG) was used: ODN 1 and ODN 8 repre...
Galvão A, Skarzynski DJ, Szóstek A, Silva E, Tramontano A, Mollo A, Mateus L, Ferreira-Dias G.Knowledge on the regulation of corpus luteum (CL) function in the mare is scarce. In this study, the presence of cytokines tumor necrosis factor alpha (TNF) and interferon gamma (IFNG), and their receptors (TNFRI, TNFRII and IFNRI), was investigated in equine CL throughout the luteal phase. The effects of TNF and IFNG on secretory function and viability of luteal cells were defined in vitro. Cytokine ligands and receptors were present in steroidogenic and endothelial cells. Protein expression for TNF was greater in mid-phase and regressing CL, while TNFRI was increased in regressing CL and TNF...
Maeda Y, Ohtsuka H, Tomioka M, Tanabe T, Nambo Y, Uematsu H, Oikawa MA.Escherichia coli(E. coli) isolated from the uterus of a Thoroughbred mare with bacterial endometritis was used to evaluate the effect of progesterone (P(4)) on the immune response of mares. Peripheral blood mononuclear cells (PBMCs) were collected from 10 nonpregnant clinically healthy adult mares (range, 4-12 years) during diestrus, four Thoroughbreds and six Hokkaido native horses. Cell proliferation and expression of cytokine mRNA, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-10, of PBMCs stimulated with E. coli and P(4) were examined in vitro. P(4) was...
Paillot R, Prowse L.The humoral immune response induced by ISCOM-matrix (Immuno Stimulating COMplex-Matrix)-adjuvanted equine influenza virus (EIV) vaccine is well documented in horses. ISCOM-matrix adjuvanted vaccines against human influenza are strong inducers of cell-mediated immunity (CMI), including T cell proliferation and virus-specific cytotoxic T cell. In the horse, the CMI response to equine influenza vaccination is less well characterised. An ISCOM-based vaccine has been shown to induce interferon gamma (IFN-γ) synthesis, a CMI marker, in the horse, but this has not been shown for the ISCOM-matrix vac...
Sun L, Adams AA, Betancourt A, Stewart JC, Liu C, Horohov DW.Interferon-gamma (IFNγ) plays an important role against viral and intracellular bacterial infections and its production is deficient in foals. Cellular proliferation provides an opportunity for de novo gene expression, though little is known about its role in regulating IFNγ expression in foals. While stimulation of foal peripheral blood mononuclear cells (PBMCs) with concanavalin A (ConA) increased the frequency of IFNγ(+) cells, the overall percentage of IFNγ(+) cells remained below that of adults. By contrast, the proliferative response of foal PBMC was significantly greater than that o...
Müller JM, Wissemann J, Meli ML, Dasen G, Lutz H, Heinzerling L, Feige K.Whole blood pharmacokinetics of intratumourally injected naked plasmid DNA coding for equine Interleukin 12 (IL-12) was assessed as a means of in vivo gene transfer in the treatment of melanoma in grey horses. The expression of induced interferon gamma (IFN-g) was evaluated in order to determine the pharmacodynamic properties of in vivo gene transduction. Seven grey horses bearing melanoma were injected intratumourally with 250 µg naked plasmid DNA coding for IL-12. Peripheral blood and biopsies from the injection site were taken at 13 time points until day 14 post injection (p.i.). Samples w...
Goodyear A, Troyer R, Bielefeldt-Ohmann H, Dow S.The Gram-negative bacterium Burkholderia mallei causes rapidly fatal illness in equines and humans when contracted by inhalation and also has the potential to be used as a bioweapon. However, little is known regarding the early innate immune responses and signaling mechanisms required to generate protection from pneumonic B. mallei infection. We showed previously that monocyte chemoattractant protein 1 (MCP-1) was a critical chemokine required for protection from pneumonic B. mallei infection. We have now extended those studies to identify key Toll-like receptor (TLR) signaling pathways, effec...
Hagen J, Hartnett C, Houchins JP, Giguère S, Kalyuzhny AE.Human and mouse immune system cells are the most frequently used specimens in ELISPOT assays. In an effect to expand the application of ELISPOT assay to other species, we developed matched antibody pairs for ready-to-use kits designed for studying the frequency of equine IFNγ- and IL-4-secreting peripheral blood mononuclear cells (PBMCs). Equine PBMCs were stimulated with either concanavalin A (Con A) or calcium ionomycin mixed with phorbol 12-myristate 13-acetate (CaI + PMA). We found that Con A, in general, had a more profound stimulating effect than CaI + PMA on IL-4 secretion, whereas bot...
Sun L, Adams AA, Page AE, Betancourt A, Horohov DW.While interferon-gamma (IFNγ) plays an important role in protection against viral and intracellular bacterial infections, its production in neonates is deficient. Exposure to environmental antigens can promote the maturation of the immune system of neonatal humans and mice. We hypothesize that exposure to high level of microbial components would increase the production of IFNγ in neonatal foals. To test this hypothesis, one group of foals was placed into stalls three times a week for 8 weeks. A second group of foals remained on pasture. Air samples were collected from the barn and pasture fo...
Pusterla N, Mapes S, Gebhart C.The cell-mediated immune response to Lawsonia intracellularis, the agent of equine proliferative enteropathy (EPE), was investigated in vaccinated and naturally infected foals. Interferon (IFN)-γ gene expression was determined in peripheral blood mononuclear cells collected from vaccinated (n=6) and control foals (n=6) every 30 days for 180 days following first vaccine administration, and from clinically affected foals (n=16) within 7-10 days of diagnosing EPE. Seroconversion (immunoperoxidase monolayer assay titer ≥60) occurred in 5/6 vaccinated foals between 60 and 90 days following the f...
Page AE, Loynachan AT, Bryant U, Stills HF, Adams AA, Gebhart CJ, Pusterla N, Horohov DW.Lawsonia intracellularis is the etiological agent of infectious intestinal hyperplasia for which several clinical diseases have been described including proliferative enteropathy (PE), intestinal adenomatosis, and ileitis. While initially recognized as the causative agent of PE in pigs, L. intracellularis is now viewed as an emerging cause of intestinal hyperplasia in a wide range of mammalian species, including horses. Equine proliferative enteropathy (EPE) has been reported worldwide though definitive diagnosis is difficult and the epidemiology of the disease remains poorly understood. Weanl...
Liburt NR, Adams AA, Betancourt A, Horohov DW, McKeever KH.Studies have demonstrated increases in mRNA expression for inflammatory cytokines following exercise in horses and have suggested those markers of inflammation may play a role in delayed onset muscle soreness. However, measurement of mRNA expression in white blood cells is an indirect method. No studies to date have documented the cytokine response to exercise directly in muscle in horses. Objective: This study tested the hypothesis that exercise increases cytokine markers of inflammation in blood and muscle. Methods: Blood and muscle biopsies were obtained from 4 healthy, unfit Standardbred m...
Sturgill TL, Strong D, Rashid C, Betancourt A, Horohov DW.Production of the Th1 cytokine interferon gamma (IFNγ) is associated with resistance to intracellular pathogens, including Rhodococcus equi. While neonatal foals are initially deficient in IFNγ production, expression of this cytokine increases throughout their first year of life. This is presumably the result of stimulation by environmental antigens including pathogen associated molecular patterns (PAMPS) signaling through toll-like receptors (TLR). This increased expression of IFNγ is likewise associated with an age-related resistance to R. equi infection. While immunostimulants containing...
Klein C, Scoggin KE, Troedsson MH.Establishment of pregnancy is critically dependent upon a precisely orchestrated embryo-maternal interaction leading to a receptive uterine environment. The up-regulation of the interferon-stimulated protein 15 kDa (ISG15) during pregnancy has been described in various species and has been hypothesized to be part of the molecular repertoire that makes the uterus receptive to conceptus development. In the current study, the expression of ISG15 and enzymes involved in ISG15ylation was examined at the mRNA and protein level in equine endometrium at Day 14 of the luteal phase and at Day 14 and 50 ...
Paillot R, Darby AC, Robinson C, Wright NL, Steward KF, Anderson E, Webb K, Holden MT, Efstratiou A, Broughton K, Jolley KA, Priestnall SL....The acquisition of superantigen-encoding genes by Streptococcus pyogenes has been associated with increased morbidity and mortality in humans, and the gain of four superantigens by Streptococcus equi is linked to the evolution of this host-restricted pathogen from an ancestral strain of the opportunistic pathogen Streptococcus equi subsp. zooepidemicus. A recent study determined that the culture supernatants of several S. equi subsp. zooepidemicus strains possessed mitogenic activity but lacked known superantigen-encoding genes. Here, we report the identification and activities of three novel ...
Wagner B, Burton A, Ainsworth D.Cytokines produced by T helper (Th) cells are important in orchestrating the immune response during health and disease. Recent reports indicated that cytokine mRNA expression in foals is often quantitatively lower than that of adult horses suggesting that foal T cells are not fully mature. Here, peripheral blood mononuclear cells from foals and adult horses were stimulated with phorbol 12-myristate 13-acetate and analyzed for intracellular interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-10 production, representing the Th1, Th2 and regulatory TR1 cell phenotypes respectively, by flow ...
Saulez MN, Godfroid J, Bosman A, Stiltner JL, Breathnach CC, Horohov DW.To determine concentrations of cytokine mRNA in horses with exercise-induced pulmonary hemorrhage (EIPH) after racing. Methods: 97 Thoroughbreds. Methods: Following tracheobronchoscopy, the severity of EIPH was graded (scale of 0 to 4), and venous blood samples were collected from 10 horses in each grade. After RNA isolation and cDNA synthesis, real-time PCR assay was conducted to detect cytokinespecific mRNA for interleukin (IL)-1, IL-6, and IL-10; interferon (INF)-gamma; and tumor necrosis factor (TNF)-alpha. Results: Neither location nor grade of EIPH affected the expression of IL-1 and INF...
Harris SP, Fujiwara N, Mealey RH, Alperin DC, Naka T, Goda R, Hines SA.Immune adult horses have CD8(+) cytotoxic T lymphocytes (CTLs) that recognize and lyse Rhodococcus equi-infected cells in an equine lymphocyte alloantigen (ELA)-A [classical major histocompatibility complex (MHC) class I]-unrestricted fashion. As protein antigens are MHC class I-restricted, the lack of restriction suggests that the bacterial antigens being recognized by the host are not proteins. The goals of this study were to test the hypothesis that these CTLs recognize unique R. equi cell-wall lipids related to mycobacterial lipids. Initial experiments showed that treatment of soluble R. e...
Saenz RA, Quinlivan M, Elton D, Macrae S, Blunden AS, Mumford JA, Daly JM, Digard P, Cullinane A, Grenfell BT, McCauley JW, Wood JL, Gog JR.A key question in pandemic influenza is the relative roles of innate immunity and target cell depletion in limiting primary infection and modulating pathology. Here, we model these interactions using detailed data from equine influenza virus infection, combining viral and immune (type I interferon) kinetics with estimates of cell depletion. The resulting dynamics indicate a powerful role for innate immunity in controlling the rapid peak in virus shedding. As a corollary, cells are much less depleted than suggested by a model of human influenza based only on virus-shedding data. We then explore...
Paillot R, Robinson C, Steward K, Wright N, Jourdan T, Butcher N, Heather Z, Waller AS.Streptococcus equi is the causative agent of strangles, the most frequently diagnosed infectious disease of horses worldwide. The disease is characterized by abscessation and swelling of the lymph nodes of the head and neck, which can literally strangle the horse to death. S. equi produces four recently acquired phage-associated bacterial superantigens (sAgs; SeeH, SeeI, SeeL, and SeeM) that share homology with the mitogenic toxins of Streptococcus pyogenes. The aim of this study was to characterize the contribution of each of these S. equi sAgs to mitogenic activity in vitro and quantify the ...
Platt R, Sponseller BA, Chiang YW, Roth JA.The cell-mediated immune (CMI) response of foals to virulent equine herpesvirus-1 (EHV-1) infection was evaluated by multi-parameter flow cytometry (FCM). Ten 7-8-month-old EHV-1 seronegative foals were infected intranasally with virulent EHV-1 and 10 foals served as uninfected controls. Blood samples were collected 6 and 7 weeks after infection to test for specific CMI responses to live heterologous EHV-1 recall antigen. The activation markers included major histocompatibility complex class II (MHC II), intracellular interferon gamma (IFN-gamma) and interleukin 4 (IL-4). The results from both...
Soboll G, Breathnach CC, Kydd JH, Hussey SB, Mealey RM, Lunn DP.The control of EHV-1 infection by cytotoxic T-cell responses (CTL) via a reduction in cell associated viremia remains an important goal in horses. Unfortunately, current vaccines are inefficient at inducing these responses. We have identified the immediate early (IE) gene of EHV-1 as a potent stimulator of virus-specific CTL responses in ponies expressing a specific MHC class I serological haplotype (A3/B2). This study was designed to determine if vaccination of A3/B2 MHC I positive ponies with the IE gene could induce protection and immune responses associated with cell mediated immunity. Pon...
Sentsui H, Wu D, Murakami K, Kondo T, Matsumura T.Recombinant equine interferon-gamma (reIFN-gamma) was prepared using a baculovirus expression system and its antiviral activity was investigated using several equine viruses. The reIFN-gamma suppressed the replication of all equine viruses used in the present experiment in horse cell cultures, but did not affect the growth of host cells at concentrations of less than 1000 u/ml. A strong antiviral effect was observed, especially against RNA viruses. Equine picornavirus, equine rhinovirus and equine arteritis virus could not be propagated at all in 100 u/ml reIFN-gamma when 100 TCID(50) of infec...
Lee J, Park JH, Min JY.The non-structural protein of influenza A virus (NS1A protein) is a multifunctional protein that antagonizes host antiviral responses and contributes to efficient viral replication during infection. However, most of its functions have been elucidated by generating recombinant viruses expressing mutated NS1 proteins that do not exist in nature. Recently, the novel H3N8 A/Equine/Kyonggi/SA1/2011 (KG11) influenza virus was isolated in Korea from horses showing respiratory disease symptoms. KG11 virus contains a naturally truncated NS gene segment with the truncation in the NS1A coding region, res...
Wagner B, Hillegas JM, Flaminio MJ, Wattrang E.Interferon-alpha (IFN-alpha) is a type I interferon that is secreted during the early stages of the innate immune response and is often induced upon infection with viral pathogens. IFN-alpha production affects multiple downstream events influencing both innate and adaptive immune responses. Here, we describe the expression of an equine rIFN-alpha/IgG4 fusion protein in mammalian cells. The anti-viral activity of rIFN-alpha/IgG4 was found to be 70-fold higher than that of a previously described IFN-gamma/IgG1 as tested by bioassay. The purified rIFN-alpha was subsequently used for the generatio...
Bridges CG, Edington N.Intrinsic phagocytosis and killing of C. albicans by equine monocytes and polymorphonuclear leucocytes (PMN) was examined during Equid Herpesvirus 1 (EHV-1) (subtypes 1 or 2) and Adenovirus infections. Monocyte function increased during EHV-1 subtype 2 and Adenovirus infection. Conversely, there was an impairment of monocyte ingestion during EHV-1 subtype 1 infection which was ascribed to virus replication in peripheral blood mononuclear cells. PMN phagocytosis was not decreased in any of the infections studied. The raised levels of haemolytic complement in animals which subsequently developed...
Mignot CC, Pirottin D, Farnir F, de Moffarts B, Molitor C, Lekeux P, Art T.The effects of strenuous exercise and ex vivo stimulation of TLR3 and TLR4 pathways on the expression of six inflammatory genes in equine pulmonary leukocytes were investigated. The genes tested were interferon-beta (IFN-β), interleukin-1-beta (IL-1β), interleukin-6 (IL-6), interferon gamma-induced protein 10 (IP-10), chemokine (c-c motif) ligand 5 (RANTES) and tumor necrosis factor-alpha (TNF-α). We hypothesized that strenuous exercise would modulate basal gene expression on one hand and modulate the response to bacterial lipopolysaccharide (LPS) and to polyinosinic:polycytidylic acid (Pol...
Jindra C, Hainisch EK, Rümmele A, Wolschek M, Muster T, Brandt S.Bovine papillomaviruses types 1 and 2 (BPV1, BPV2) commonly induce skin tumours termed sarcoids in horses and other equids. Sarcoids seriously compromise the health and welfare of affected individuals due to their propensity to resist treatment and reoccur in a more severe form. We have developed influenza (Flu) A and B virus vectors that harbour a truncated NS1 gene (iNS) assuring interferon induction and co-express shuffled BPV1 E6 and E7 antigens for sarcoid immunotherapy. In a safety trial involving 12 healthy horses, intradermal administration of iNSA/E6E7equ and iNSB/E6E7equ was well tol...
Svansson V, Roelse M, Olafsdóttir G, Thorsteinsdóttir L, Torfason EG, Torsteinsdóttir S.Horses are hosts to two types of gammaherpesviruses, equine herpes virus (EHV) 2 and 5. While EHV-2 is ubiquitous in adult horses, EHV-5 has been less frequently described. Due to strong serological cross-reactivity, EHV-2 and -5 cannot be discriminated in broad spectrum antibody tests and are thus commonly referred to as gamma-EHV. Total IgG and IgG subclass response against gamma-EHV were determined in serum from 41 healthy Icelandic horses, thereof 20 adults, 10 foals aged 10 months, and 11 foals aged 1-4 months. Additionally, in 10 of the adult horses, interferon (IFN)-gamma and interleuki...
Wattrang E, Palm AK, Wagner B.Synthetic oligodeoxyribonucleotides (ODN) may prove useful immune modulators in equine medicine. It is however important to assess the effects of each specific ODN in the species it is intended to be used in. The present study therefore aimed to evaluate some ODN for induction of cytokine production; i.e. type I interferons (IFN), IFN-γ, tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), and proliferation of equine peripheral blood mononuclear cells (PBMC). A panel of four ODN containing unmethylated cytosine-guanosine sequences (CpG) was used: ODN 1 and ODN 8 repre...
Spencer JA, Ellison SE, Guarino AJ, Blagburn BL.Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome seen in horses from the Americas and is mainly caused by Sarcocystis neurona. Cell-mediated immune responses to mitogens have been shown to be reduced in horses with EPM, although it is not known whether the parasite causes this immunosuppression or if the immunosuppression is required for disease manifestation. Recently, a 29-kDa surface antigen from S. neurona merozoites was identified as being highly immunodominant on Western blot. This antigen has been sequenced and cloned, and the expressed protein has been named SnSAG1. Is...
Davidson AJ, Hodgkinson JE, Proudman CJ, Matthews JB.To investigate cytokine responses in cyathostomin infection, we quantified mucosal interleukin-4 (IL-4), interleukin-10 (IL-10), tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma by reverse transcriptase-competitive polymerase chain reaction. The analysis was performed on large intestinal wall samples obtained from six anatomical sites spanning the caecum and colon of 17 naturally exposed horses. The numbers of developing larvae (DL) and early third stage larvae (EL3) were ascertained using transmural illumination and pepsin digestion techniques, respectively. Levels of each cytoki...
Nielsen MK, Betancourt A, Lyons ET, Horohov DW, Jacobsen S.Cyathostomins can cause a severe inflammation of equine large intestine characterized by substantial ventral edema and pronounced protein loss. Anthelmintic treatment of horses can result in a localized inflammatory response in the colonic mucosa of clinically normal horses. The aim of this study was to evaluate the systemic inflammatory response of ponies naturally infected with cyathostomins to single dose representatives of three anthelmintic drug classes, namely, oxibendazole, pyrantel pamoate, and moxidectin. Thirty ponies aged between 1 and 18 years of age were allocated to one of three ...
Tsuchiya T, Hobo S, Endo Y, Narita S, Sakamoto K.To evaluate effects of a single dose of enrofloxacin (5 mg/kg, IV) on body temperature and tracheobronchial neutrophil count in healthy Thoroughbreds premedicated with interferon-α and undergoing long-distance transportation. Methods: 32 healthy Thoroughbreds. Methods: All horses received interferon-α (0.5 U/kg, sublingually, q 24 h) as an immunologic stimulant for 2 days before transportation and on the day of transportation. Horses were randomly assigned to receive enrofloxacin (5 mg/kg, IV, once; enrofloxacin group) or saline (0.9% NaCl) solution (50 mL, IV, once; control group) ≤ 1 hou...
Lohmann KL, Lopez AM, Manning ST, Marques FJ, Brownlie R, Allen AL, Sangster AE, Mutwiri G, Gerdts V, Potter A, Townsend HG.We evaluated the immunogenic and protective potential of a recombinant VapA/CpG oligodeoxynucleotide (ODN) 2395 vaccine in neonatal foals undergoing experimental Rhodococcus equi challenge. Foals (n = 8) were vaccinated by intramuscular injection on days 1 and 15 of the study; control foals (n = 7) received a phosphate-buffered saline (PBS) solution. All foals were challenged by intrabronchial administration of 5 × 10⁶ R. equi 103⁺ on day 29. Bronchoalveolar lavages were done on days 15, 29, and 36 and total cell count, differential cell count, rVapA-stimulated cell proliferation and inte...
Baker CB, Adams MH, McDowell KJ.Horse conceptuses were collected on Days 13, 15, 20 and 25 after ovulation. Whole conceptuses (Days 13 and 15) or extra-embryonic membranes (Days 20 and 25) were homogenized and poly-adenylated RNA (poly A RNA) was isolated by binding to oligo (dT)-cellulose. Poly A RNA (1 microgram/well) was separated by size on a denaturing 1% agarose gel and blotted onto nitrocellulose filters (northern blotting). DNA probes were prepared from plasmids containing equine alpha 1, omega 1 and omega 2 interferons and human beta actin. The presence of messenger RNA (mRNA) was detected by specific hybridization ...
Pusterla N, Wilson WD, Conrad PA, Mapes S, Leutenegger CM.To determine gene transcription for cytokines in nucleated cells in CSF of horses without neurologic signs or with cervical stenotic myelopathy (CSM), West Nile virus (WNV) encephalitis, equine protozoal myeloencephalitis (EPM), or spinal cord trauma. Methods: 41 horses (no neurologic signs [n = 12], CSM [8], WNV encephalitis [9], EPM [6], and spinal cord trauma [6]). Methods: Total RNA was extracted from nucleated cells and converted into cDNA. Gene expression was measured by use of real-time PCR assay and final quantitation via the comparative threshold cycle method. Results: Cytokine genes ...
Samimi AS, Samimi K, Karimiafshar M, Tajik J.The objective of this study was to comparatively evaluate the anti-inflammatory effects of intravenous administration of insulin (in different doses) and flunixin on physiological variables, acute-phase responses, and cardiovascular biomarkers during inflammatory phase which was induced by Escherichia coli lipopolysaccharide (LPS) serotype O55:B5 in miniature donkeys. A total of twenty-four clinically healthy male adult miniature donkeys aged 5 ± 1 year and weighing 120 ± 10 kg were studied. The animals were assigned randomly to four experimental groups (three treatment and one positive co...
Deniz Ö, Ekinci G, Onmaz AC, Derelli FM, Fazio F, Aragona F, Hoven RVD.Rhodococcus equi (R. equi), a gram-positive facultative intracellular pathogen, is a common cause of pneumonia in foals and represents a major cause of disease and death. The aim of the present study was to investigate the time-depended changes in White Blood Cells (WBC), basophils (Baso), neutrophils (Neu), lymphocytes (Lymf), monocytes (Mon), eosinophils (Eos), platelet (PLT) counts, fibrinogen (Fbg) concentration, interferon (IFN-α, IFN-γ) and interleukins (IL-2 and IL-10) in foals with clinical R. equi pneumonia. The main treatment was with azithromycin-rifampicin for 14 days. Blood was ...
Witkowska-Piłaszewicz O, Pingwara R, Szczepaniak J, Winnicka A.Clenbuterol, the β2-adrenoceptor agonist, is gaining growing popularity because of its effects on weight loss (i.e., chemical liposuction). It is also popular in bodybuilding and professional sports, due to its effects that are similar to anabolic steroids. However, it is prohibited by anti-doping control. On the other hand, it is suggested that clenbuterol can inhibit the inflammatory process. The cells from 14 untrained and 14 well-trained race horses were collected after acute exercise and cultured with clenbuterol. The expressions of CD4, CD8, FoxP3, CD14, MHCII, and CD5 in PBMC, and reac...
Adamič N, Prpar Mihevc S, Blagus R, Kramarič P, Krapež U, Majdič G, Viel L, Hoffman AM, Bienzle D, Vengust M.Severe equine asthma (SEA) is a common chronic respiratory disease and a significant health and well-being problem in horses. Current therapeutic strategies improve pulmonary function and clinical signs in some horses, but in the long-term, return to full athletic function appears to be rare. The aim of this study was to assess the safety and the effect of intrabronchial administration of adipose-derived mesenchymal stem cells (AD-MSC) on pulmonary inflammatory and clinical parameters in horses with SEA. This was a randomized controlled trial. Twenty adult horses diagnosed with SEA were random...
Klein C, Scoggin KE, Troedsson MH.Establishment of pregnancy is critically dependent upon a precisely orchestrated embryo-maternal interaction leading to a receptive uterine environment. The up-regulation of the interferon-stimulated protein 15 kDa (ISG15) during pregnancy has been described in various species and has been hypothesized to be part of the molecular repertoire that makes the uterus receptive to conceptus development. In the current study, the expression of ISG15 and enzymes involved in ISG15ylation was examined at the mRNA and protein level in equine endometrium at Day 14 of the luteal phase and at Day 14 and 50 ...
Niedźwiedź A, Borowicz H, Kubiak K, Nicpoń J, Skrzypczak P, Jaworski Z, Cegielski M, Nicpoń J.Recurrent airway obstruction (RAO) represents a serious health problem and is traditionally classified as an allergic disease, where contact with an antigen can induce clinical airway inflammation, bronchial hyper-responsiveness and reversible airway obstruction. Previous studies have demonstrated the presence of the Th2 response in the lungs of human patients with asthma and horses with heaves. These cells are involved in the production of cytokines which regulate the synthesis of immunoglobulins. 40 horses were evaluated: 30 horses with RAO and 10 healthy animals. The expression levels of in...
Rütten S, Schrödl W, Abraham G.Glucocorticoids are important drugs in the treatment of many inflammatory, autoimmune and allergic diseases in humans and animals. We investigated the effects of hydrocortisone and dexamethasone on TNF-α, IL-1Ra and INF-γ release in stimulated whole blood cell culture from healthy horses. Whole blood cell cultures proved to be useful for the characterization of the anti-inflammatory properties of new drugs. Diluted equine whole blood was exposed to lipopolysaccharide (LPS) and PCPwL (a cocktail consisting of phythemagglutinin E, concanavalin A, pokeweed mitogen and lipopolysaccharide) in the...
Schnabel CL, Babasyan S, Freer H, Wagner B.C-X-C motif ligand 10 (CXCL10) is a pro-inflammatory chemokine and has been extensively evaluated in people and mice. In horses, CXCL10 and its involvement in host immunity has rarely been analyzed due to the lack of specific antibodies. We generated a mAb specific for the equine chemokine CXCL10 using hybridoma technology. Antibody specificity was confirmed by intracellular staining and flow cytometric analysis of Chinese Hamster Ovary (CHO) cells expressing equine rCXCL10, while CHO cells expressing equine rCXCL9 were not detected. Native CXCL10 expression in PBMC from horses of different ag...
Page AE, Loynachan AT, Bryant U, Stills HF, Adams AA, Gebhart CJ, Pusterla N, Horohov DW.Lawsonia intracellularis is the etiological agent of infectious intestinal hyperplasia for which several clinical diseases have been described including proliferative enteropathy (PE), intestinal adenomatosis, and ileitis. While initially recognized as the causative agent of PE in pigs, L. intracellularis is now viewed as an emerging cause of intestinal hyperplasia in a wide range of mammalian species, including horses. Equine proliferative enteropathy (EPE) has been reported worldwide though definitive diagnosis is difficult and the epidemiology of the disease remains poorly understood. Weanl...
Sun L, Gong Z, Oberst EJ, Betancourt A, Adams AA, Horohov DW.While born with a limited production, foals' interferon-gamma (IFN-γ) expression increases after birth. The underlying mechanisms remain unknown. DNA methylation is considered to be involved. Therefore, the DNA methylation status of the Ifng promoter in CD4(+) cells from neonatal foal was determined using a methylation-specific PCR (MSP), and its relevance to IFN-γ mRNA expression was estimated. The effect of environment on the DNA methylation was also evaluated by comparing ponies that were kept in a barn versus those on pasture. The DNA in the Ifng promoter was hypermethylated and its deme...
Davis EG, Zhang Y, Tuttle J, Hankins K, Wilkerson M.West Nile virus (WNV) is a single-stranded, enveloped RNA virus capable of causing encephalitic disease in horses. Unvaccinated horses are at risk for developing WNV disease in endemic geographic regions. Effective vaccination reduces disease frequency and diminishes disease severity in vaccinated individuals that become infected with WNV. Recent data indicate CD4+ lymphocytes are required for effective protection against disease; in particular, cross talk between CD4+ and CD8+ lymphocytes must be functional. The objective of this project was to investigate immune responses in horses throughou...
Davis EG, Rush BR, Blecha F.Immunomodulation with Propionibacterium acnes is used for prophylaxis of respiratory disease or in horses suffering from chronic pulmonary inflammation; however, the mechanism for this response is poorly understood. Semiquantitative reverse transcriptase-polymerase chain reaction assays were used to evaluate gene expression of interleukin (IL)-2, IL-10, interferon (IFN)-gamma, and NK-lysin in healthy horses treated with P. acnes. Findings in the study indicated that horses treated with a P. acnes-based immunomodulator exhibited increased IFN-gamma and NK-lysin gene expression in peripheral blo...
Zarski LM, Vaala WE, Barnett DC, Bain FT, Soboll Hussey G.Equine herpesvirus 1 (EHV-1) ubiquitously infects horses worldwide and causes respiratory disease, abortion, and equine herpesvirus myeloencephalopathy. Protection against EHV-1 disease is elusive due to establishment of latency and immune-modulatory features of the virus. These include the modulation of interferons, cytokines, chemokines, antigen presentation, and cellular immunity. Because the modulation of immunity likely occurs at the site of first infection-the respiratory epithelium, we hypothesized that the mucosal influenza vaccine Flu Avert I.N. (Flu Avert), which is known to stimulat...
Ryan C, Giguère S, Hagen J, Hartnett C, Kalyuzhny AE.Peripheral blood mononuclear cells (PBMCs) were obtained from 6 foals <1 week of age, 6 foals between 3 and 4 months of age, and 10 adult horses. PBMCs were stimulated with concanavalin A (ConA) or calcium ionomycin-phorbol myristate acetate (CaI-PMA) and the frequency of interferon IFN-gamma and IL-4 secreting cells was measured using an equine-specific ELISPOT assay. The number of IFN-gamma secreting cells was significantly lower in both groups of foals than in adult horses regardless of the mitogen used for stimulation. The number of IFN-gamma secreting cells was significantly higher in ...
Hu Z, Wu X, Ge J, Wang X.Type I interferons (IFNs) play important roles in the defense of host cells against viral infection by inducing the expression of a diverse range of antiviral factors. IFNs from different animals likely share similar features with human IFNs, and some of them have cross-species activities. Equine IFN-α was proved effective in both equine and human cells. However, the previous studies mostly focused on the inhibition of virus induced cytopathic effects. In this study, we used virus-specific assays to demonstrate the antiviral activities of equine IFN-α1 in both equine and human cells. Equine ...
