The inflammatory response in horses is a complex physiological process that occurs when the immune system reacts to harmful stimuli such as pathogens, damaged cells, or irritants. This response is characterized by the activation of various immune cells, the release of signaling molecules, and the production of inflammatory mediators. In horses, the inflammatory response involves both innate and adaptive immune mechanisms, which work together to eliminate the source of harm and initiate tissue repair. Key components of the equine inflammatory response include cytokines, chemokines, and leukocytes, which coordinate the body's defense and healing processes. This page gathers peer-reviewed research studies and scholarly articles that explore the mechanisms, regulation, and implications of the inflammatory response in equine health and disease.
Zarski LM, Giessler KS, Jacob SI, Weber PSD, McCauley AG, Lee Y, Soboll Hussey G.Equine herpesvirus-1 is the cause of respiratory disease, abortion, and equine herpesvirus myeloencephalopathy (EHM) in horses worldwide. EHM affects as many as 14% of infected horses and a cell-associated viremia is thought to be central for EHM pathogenesis. While EHM is infrequent in younger horses, up to 70% of aged horses develop EHM. The aging immune system likely contributes to EHM pathogenesis; however, little is known about the host factors associated with clinical EHM. Here, we used the "old mare model" to induce EHM following EHV-1 infection. Peripheral blood mononuclear cells (PBMC...
Fedorka CE, Ball BA, Walker OF, McCormick ME, Scoggin KE, Kennedy LA, Squires EL, Troedsson MHT.Equine abortions are attributed to both infectious and noninfectious causes. Clinical extrapolations are often made from the experimental model for ascending placentitis towards other causes of fetal compromise, including various markers of inflammation, including the cytokines IL-2, 5, IL-6, IL-10, IFNγ, and TNF. It is unknown if these cytokine changes are noted under field conditions, or if they increase preceding other pregnancy related complications. To assess this, Thoroughbred mares (n = 702) had weekly blood obtained beginning in December 2013 and continuing until parturition. Fet...
Page AE, Adam E, Arthur R, Barker V, Franklin F, Friedman R, Grande T, Hardy M, Howard B, Partridge E, Rutledge M, Scollay M, Stewart JC, Vale A....The ability to identify horses at risk for catastrophic injuries continues to be a pressing issue for the racing industry, especially given recent events in North America. Objective: Since most catastrophic injuries occur in areas of existing pathology and this pathology is likely to elicit an inflammatory response, it was hypothesised that analysis of messenger RNA (mRNA) expression would detect significant changes in select genes in horses at risk for a catastrophic injury. Methods: Prospective cohort study. Methods: Five racing jurisdictions across the United States participated in this stu...
Fedorka CE, Scoggin KE, El-Sheikh Ali H, Loux SC, Dini P, Troedsson MHT, Ball BA.Ascending placentitis is the leading cause of abortion in the horse. Interleukin (IL)-6 is considered predictive of placental infection in other species, but little is understood regarding its role in the pathophysiology of ascending placentitis. Sub-acute ascending placentitis was induced via trans-cervical inoculation of S zooepidemicus, and various fluids/serum/tissues collected 8 days later. Concentrations of IL-6 were detected within fetal fluids and serum in inoculated (n = 6) and control (n = 6) mares. RNASeq was performed on the placenta (endometrium and chorioallantois) to asses...
Fikes KK, Coverdale JA, Leatherwood JL, Campbell JM, Welsh TH, Hartz CJ, Goehring M, Millican AA, Bradbery AN, Wickersham TA.Twenty-seven mature Quarter horses were used in a randomized design to determine the effects of bioactive protein supplementation on gait kinematics and systemic inflammatory markers in a 34-d trial. Treatments consisted of oral doses of 230 g/d of pelleted supplements containing 0 g (CON; = 9), 40 g of bioactive protein (40BP; = 9; LIFELINE, APC, LLC, Ankeny, IA), and 80 g of bioactive protein (80BP; = 9) daily. Horses were fed a commercial concentrate at 0.5% BW (as-fed) and received coastal bermudagrass () hay daily. On day 33, horses consistent in exercise (CON, = 6; 40BP, = 8; 80BP,...
Jaafar N, Khoueiry M, Khoury SJ, Makki A.Spinal neurosarcoidosis is a rare disease that can manifest as myelopathy, radiculopathy, or cauda equine syndrome. Spinal epidural lipomatosis is also a rare condition resulting from overgrowth of epidural fat tissue causing compressive myelopathy. To our knowledge, there are no reports linking epidural lipomatosis and spinal neurosarcoidosis. . We describe a case of progressive myelitis in the presence of concomitant spinal neurosarcoidosis and epidural lipomatosis which was a challenging diagnosis with complete response to treatment after addressing both diseases. Both etiologies are inflam...
Bordin AI, Cohen ND, Giguère S, Bray JM, Berghaus LJ, Scott B, Johnson R, Hook M.Pneumonia caused by the intracellular bacterium Rhodococcus equi is an important cause of disease and death in immunocompromised hosts, especially foals. Antibiotics are the standard of care for treating R. equi pneumonia in foals, and adjunctive therapies are needed. We tested whether nebulization with TLR agonists (PUL-042) in foals would improve innate immunity and reduce the severity and duration of pneumonia following R. equi infection. Neonatal foals (n = 48) were nebulized with either PUL-042 or vehicle, and their lung cells infected ex vivo. PUL-042 increased inflammatory cytokines...
Pasch L, Schmidt A, King W.The use of autologous blood processing tools including platelet-rich plasma (PRP) devices is increasingly widespread in veterinary medicine. In equine reproduction, a number of studies have explored the effects of intrauterine infusion of PRP on persistent mating-induced endometritis. Artificial insemination with thawed frozen semen incites an intrauterine inflammatory response and we sought to extend the applications of intrauterine PRP to normal mares being inseminated with frozen semen. We investigated a subset of our normal breeding population to observe the clinical effects of prebreeding...
Degroote RL, Deeg CA.Horses worldwide suffer from equine recurrent uveitis (ERU), an organ-specific, immune-mediated disease with painful, remitting-relapsing inflammatory attacks alternating with periods of quiescence, which ultimately leads to blindness. In course of disease, both eyes can eventually be affected and since blind horses pose a threat to themselves and their surroundings, these animals have to be killed. Therefore, this disease is highly relevant for veterinary medicine. Additionally, ERU shows strong clinical and pathological resemblance to autoimmune uveitis in man. The exact cause for the onset ...
Tukia E, Wagner B, Vainio K, Mönki J, Kareskoski M.Postpartum metritis in mares is a life-threatening condition associated with severe clinical signs due to endotoxemia, and it is often followed by complications such as laminitis. Repeated large-volume uterine lavages are commonly recommended as a part of the treatment protocol to remove endotoxin-laden contents from the uterus. It has, however, also been suggested that lavages may increase the uptake of endotoxin into the circulation, leading to a deterioration of clinical signs. Endotoxemia is associated with the release of a multitude of inflammatory mediators regulating the immune response...
Ehrmann C, Engel J, Moritz A, Roscher K.In addition to maintaining hemostasis, platelets have an important role in modulating innate and adaptive immune responses. A low platelet count has been found to be a negative prognostic factor for survival in humans and horses with critical illnesses, such as sepsis or systemic inflammatory response syndrome (SIRS). Decreased platelet aggregation, caused by in vivo activation, has been found in human patients with severe sepsis. In our prospective controlled study, we assessed platelet biology in blood samples from 20 equine SIRS cases and 120 healthy control horses. Platelet variables such ...
El-Sheikh Ali H, Dini P, Scoggin K, Loux S, Fedorka C, Boakari Y, Norris J, Esteller-Vico A, Kalbfleisch T, Ball B.Improved understanding of the molecular mechanisms underlying ascending equine placentitis holds the potential for the development of new diagnostic tools and therapies to forestall placentitis-induced preterm labor. The current study characterized the equine placental transcriptome (chorioallantois [CA] and endometrium [EN]) during placentitis (placentitis group, n = 6) in comparison to gestationally-matched controls (control group, n = 6). Transcriptome analysis identified 2953 and 805 differentially expressed genes in CA and EN during placentitis, respectively. Upstream regulator analys...
Diaz-Jimenez M, Rota A, Dorado J, Consuegra C, Pereira B, Camillo F, Panzani D, Fanelli D, Tesi M, Monaco D, Hidalgo M.Sperm vitrification has been recently developed, but fertility trials have not been performed yet in equine species. In this study, a new warming technique for vitrified donkey semen was developed and the uterine inflammatory response and fertility were compared to conventional freezing. In Experiment 1, sperm was vitrified in straws and warmed in 3 ml of extender or in a water bath at: 37 °C/30 s; 43 °C/10 s; and 60 °C/5 s. Sperm motility, plasma and acrosome membranes and DNA integrity were compared between treatments. In Experiment 2, jennies were inseminated twice (500 Ã...
Cassimeris L, Engiles JB, Galantino-Homer H.Supporting Limb Laminitis (SLL) is a painful and crippling secondary complication of orthopedic injuries and infections in horses, often resulting in euthanasia. SLL causes structural alterations and inflammation of the interdigitating layers of specialized epidermal and dermal tissues, the lamellae, which suspend the equine distal phalanx from the hoof capsule. Activation of the interleukin-17A (IL-17A)-dependent inflammatory pathway is an epidermal stress response that contributes to physiologic cutaneous wound healing as well as pathological skin conditions. As a first test of the hypothesi...
Brown KA, Davidson EJ, Johnson AL, Wulster KB, Ortved K.Standing cone beam computed tomography (CT) provides cross-sectional imaging of the caudal cervical articular process joints (CAPJs) in the sedated horse, though the clinical implications of osteoarthritis (OA) identified on CT in this location are unknown. Increases in concentrations of intra-synovial cytokines could lend support to the clinical significance of CAPJ OA identified on this imaging modality. Objective: Investigate the presence and concentration of intra-synovial inflammatory cytokines in CAPJs with and without standing cone beam CT evidence of OA using an equine specific multipl...
Menarim BC, Gillis KH, Oliver A, Ngo Y, Werre SR, Barrett SH, Rodgerson DH, Dahlgren LA.Synovitis is a major component of osteoarthritis and is driven primarily by macrophages. Synovial macrophages are crucial for joint homeostasis (M2-like phenotype), but induce inflammation (M1-like) when regulatory functions become overwhelmed. Macrophage phenotypes in synovium from osteoarthritic and healthy joints are poorly characterized; however, comparative knowledge of their phenotypes during health and disease is paramount for developing targeted treatments. This study compared patterns of macrophage activation in healthy and osteoarthritic equine synovium and correlated histology with ...
Witkowska-Piłaszewicz O, Pingwara R, Winnicka A.Physical activity has an influence on a variety of processes in an athlete's organism including the immune system. Unfortunately, there is a lack of studies regarding racehorse immune cells, especially when the horse model is compared to human exercise physiology. The aim of the study was to determine changes in immune cell proliferation, lymphocyte populations, and monocyte functionality in trained and untrained racehorses after exercise. In this study, field data were collected. The cells from 28 racehorses (14 untrained and 14 well-trained) were collected before and after exercise (800 m at...
Davis KU, Sheats MK.Asthma is a common and debilitating chronic airway disease that affects people and horses of all ages worldwide. While asthma in humans most commonly involves an excessive type 2 immune response and eosinophilic inflammation, neutrophils have also been recognized as key players in the pathophysiology of asthma, including in the severe asthma phenotype where neutrophilic inflammation predominates. Severe equine asthma syndrome (sEAS) features prominent neutrophilic inflammation and has been increasingly used as a naturally occurring animal model for the study of human neutrophilic asthma. This...
Anderson SL, Duke-Novakovski T, Robinson AR, Townsend HGG, Singh B.The objective of this study was to determine the effect of pulmonary intravascular macrophage depletion on systemic inflammation and ex vivo neutrophil apoptosis using an experimental model of intestinal ischemia and reperfusion injury in horses. Neutrophils were isolated before and after surgery from horses that were randomized to three treatment groups, namely, sham celiotomy (CEL, = 4), intestinal ischemia and reperfusion (IR, = 6), and intestinal ischemia and reperfusion with gadolinium chloride treatment to deplete pulmonary intravascular macrophages (PIMs, IRGC, = 6). Neutrophil apopt...
Gugliandolo E, Crupi R, Biondi V, Licata P, Cuzzocrea S, Passantino A.Although inflammation is an important physiological response, it plays a prominent role in several diseases across the mammalian species. In horses, in particular, inflammation secondary to bacterial infection or translocation is one of the most frequent causes of morbidity and mortality. Research in new molecules with anti-inflammatory and immunomodulatory proprieties and safe use profile is constantly an active field; natural compounds are an important source of molecules with peculiar properties such as antioxidants, anti-inflammatory and immune modulating. Silibinin, a natural polyphenolic...
Kilcoyne I, Nieto JE, Watson JL, Galuppo LD, Borjesson DL.Endotoxemia is a leading cause of morbidity and mortality in the equine industry, with colic being the most common cause of endotoxemia in horses. The objective of this study was to evaluate the safety and potential efficacy of a single dose of allogeneic equine bone marrow derived mesenchymal stem cells (BM-MSCs) in horses after the IV administration of lipopolysaccharide (LPS). Six horses were administered an IV infusion of 30 ng/kg LPS (O55:B5 Escherichia coli) in 500 ml saline over 30 min. Immediately after infusion test horses (n = 3) were administered 100 × 10 allogeneic BM-MSCs diluted...
Wang X, Ji Y, Su J, Xue Y, Xi H, Wang Z, Bi L, Zhao R, Zhang H, Yang L, Guo Z, Guan Y, Feng X, Sun C, Lei L, Ur Rahman S, Dong J, Han W, Gu J. subsp. serovar Abortusequi is a frequently reported pathogen causing abortion in mares. In this study, the preventive and therapeutic effects of phage P SAE-01E2 against Abortusequi in a mouse model of abortion were investigated. Phage P SAE-01E2 was stable at different temperatures (4 to 70°C) and pH values (pH 4 to 10) and could lyse the majority of the serogroup O:4 and O:9 strains tested (25/28). There was no lysogeny-related, toxin, or antibiotic resistance-related gene in the genome of P SAE-01E2. All of these characteristics indicate that P SAE-01E2 has the potential for use in pha...
Nocera I, Bonelli F, Meucci V, Rinnovati R, Spadari A, Intorre L, Pretti C, Sgorbini M.Literature on the protein carbonyl content (PCC) evaluation in horses is scarce, thus the aims were to evaluate the PCC in healthy and SIRS (Systemic Inflammatory Response Syndrome) horses and to investigate the performances of PCC in terms of sensitivity, specificity, and likelihood ratio in identifying SIRS positive and negative horses. A total of 72 adult horses were included. All the horses underwent to a complete physical examination, blood analysis, and were evaluated for the SIRS status. Blood samples were collected once in healthy horses and at admission time, then 24, 48, 72, and 96 h...
Alonso JM, Martins ES, Peccinini RG, Rosa GS, Guerra ST, Ribeiro MG, Santos B, GarcÃa HDM, Watanabe MJ, Takahira RK, Rodrigues CA, Alves ALG....Intraperitoneal ceftriaxone administration in healthy horses results in high and prolonged peritoneal concentrations. Recent findings suggest that intraperitoneal ceftriaxone might increase survival rates in horses affected by peritonitis. The present study aimed to evaluate plasma and peritoneal concentrations of ceftriaxone after intraperitoneal administration in horses with septic peritonitis. Twenty-six horses presenting clinical, laboratorial, and sonographic findings compatible with the disease were included. All horses received daily intraperitoneal ceftriaxone (25Â mg/kg bwt) in additi...
Pringle J, Venner M, Tscheschlok L, Waller AS, Riihimäki M.Difficulty in detection of silent carriers of Streptococcus equi is a key reason for its continued spread to immunologically naïve groups of horses. Objective: To determine whether clinical examination, markers of inflammation, or serology differentiate silent carriers of S. equi in recovered comingled horses. Methods: Ninety-eight warmblood yearlings and 72 unaffected mares on a large breeding farm (outbreak A), 38 mature Icelandic horses at a riding stable (outbreak B), and 27 mixed breed horses at a boarding stable (outbreak C). Methods: Prospective observational study 6 months to 2 year...
Contreras-Aguilar MD, Tvarijonaviciute A, Monkeviciene I, MartÃn-Cuervo M, González-Arostegui LG, Franco-MartÃnez L, Cerón JJ, Tecles F....Measurement of adenosine deaminase (ADA) can provide information about cell-mediated immunity. This report's objective was to study the enzymatic activity of total ADA (tADA) and its isoenzymes ADA1 and ADA2 in canine, equine, porcine, and bovine serum and saliva and their changes in different inflammatory situations in each species. Besides, an automated method for ADA2 measurement was developed and validated. Results: tADA was present in serum and saliva of healthy animals of the four species. Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) concentration of 0.47 mM was needed for ADA1 inhibit...
Jaworska J, Ropka-Molik K, Kowalczyk-Zięba I, Boruszewska D, Wocławek-Potocka I, Siemieniuch M.Physiological parturition is characterized by sterile, inflammatory-like processes. During parturition, the placenta expresses various proinflammatory mediators, such as chemokines and IL-17. Nevertheless, inflammatory processes present in the parturient mare are poorly characterized. The aim of this study was to investigate the expression of selected chemokines and IL-17 in the allantochorion and the endometrium of mares that retained fetal membranes (RFM) and expelled them physiologically. We hypothesized that the expression of these mediators may be altered in the placenta of mares with RFM...
Albornoz A, Alarcon P, Morales N, Uberti B, Henriquez C, Manosalva C, Burgos RA, Moran G.The present work characterized the metabolomic profile of bronchoalveolar lavage fluid (BALF) in healthy horses, experimentally-induced airway inflammation by lipopolysaccharide (LPS) nebulization, and naturally-occurring asthma (n = 3 in each group). All animals underwent clinical and upper airway endoscopic examinations, and bronchoalveolar lavage. BALF supernatant samples were subjected to metabolic analysis based on gas chromatography-mass spectrometry (GC-MS). Overall, 67 peaks were obtained from BALF GC-MS analysis, corresponding to 53 metabolites which were categorized according to ch...
Karagianni AE, Lisowski ZM, Hume DA, Scott Pirie R.The mononuclear phagocyte system (MPS) is a family of cells of related function that includes bone marrow progenitors, blood monocytes and resident tissue macrophages. Macrophages are effector cells in both innate and acquired immunity. They are a major resident cell population in every organ and their numbers increase in response to proinflammatory stimuli. Their function is highly regulated by a wide range of agonists, including lymphokines, cytokines and products of microorganisms. Macrophage biology has been studied most extensively in mice, yet direct comparisons of rodent and human macro...
Wilmink JM, Veenman JN, van den Boom R, Rutten VP, Niewold TA, Broekhuisen-Davies JM, Lees R, Armstrong S, van Weeren PR, Barneveld A.Wound healing proceeds faster in ponies than in horses and complications during healing, such as wound infection, occur less frequently in ponies. Earlier studies suggested that this difference might be related to differences in the initial post traumatic inflammatory response. Objective: That polymorphonuclear leucocyte (PMN) function and profiles of humoral factors in local inflammatory processes are different in horses and ponies. Methods: PMNs were isolated from venous blood of horses and ponies. Chemotaxis and reactive oxygen species (ROS) production was determined. Tissue cages were impl...
van den Boom R, Wilmink JM, O'Kane S, Wood J, Ferguson MW.Wound healing in horses is often complicated by wound infection, exuberant granulation tissue, and hypertrophic scars, especially when wounds are located on the limbs. Wound healing in ponies is less problematic, characterized by a greater degree of wound contraction and a more intense initial inflammatory response. Because both processes are influenced by transforming growth factor-beta (TGF-beta), it was hypothesized that the better wound healing in ponies was associated with different TGF-beta profiles. A series of small wounds was created on the distal limbs and hindquarters of ponies and ...
Covaleda L, Fuller FJ, Payne SL.Equine infectious anemia virus (EIAV) infection is distinctive in that it causes a rapid onset of clinical disease relative to other retroviruses. In order to understand the interaction dynamics between EIAV and the host immune response, we explored the effects of EIAV and its S2 protein in the regulation of the cytokine and chemokine response in macrophages. EIAV infection markedly altered the expression pattern of a variety of pro-inflammatory cytokines and chemokines monitored in the study. Comparative studies in the cytokine response between EIAV(17) and EIAV(17DeltaS2) infection revealed ...
Dern K, van Eps A, Wittum T, Watts M, Pollitt C, Belknap J.Although continuous digital hypothermia (CDH) protects lamellae from injury in the oligofructose (OF) model of sepsis-related laminitis (SRL), conflicting results exist from these studies regarding effects of CDH on lamellar inflammatory events. Objective: To determine the effect of CDH on lamellar inflammatory events in normal and OF-treated horses when instituted at a clinically relevant time point (onset of clinical signs of sepsis in this model). Methods: Standardbred geldings (n = 15) aged 3-11 years were used. Methods: In a randomized, controlled discovery study, animals were administ...
Belknap JK.The black walnut extract (BWE) model was developed after the discovery that horses bedded on shavings from black walnut trees commonly developed laminitis. The first investigators that consistently induced laminitis with black walnut shavings established that it was only the heartwood of the tree that induced laminitis. The BWE model of laminitis has allowed investigators to determine many of the early pathologic signaling events likely to occur in the developmental and acute clinical stages of the disease process, and has brought inflammatory injury to the forefront of laminitis research. The...
Mendoza L, Villalobos J, Calleja CE, Solis A.Two vaccines to treat phythiosis insidiosi in horses were evaluated in 71 Costa Rican horses between 1982 to 1988. One vaccine used a cell-mass (CMV) as antigen and the other a soluble concentrated antigen (SCAV). Both vaccines cured horses infected with Pythium insidiosum (p value approximately 14%). The age of lesions prior to vaccination was important in the response of the horses to immunotherapy. All horses with lesions 0.5 months or less in duration were cured regardless of the vaccine used. Horses with lesions two or more months old did not respond to either vaccine. The age of the hors...
Miller RI, Campbell RS.Pythiosis (204 cases, 77%), basidiobolomycosis (48 cases, 18%), and conidiobolomycosis (14 cases, 5%) were diagnosed morphologically from 266 horses with phycomycosis. All lesions were cutaneous ulcerative granulomas and three horses with pythiosis had metastatic lesions in regional lymph nodes. Lesions of pythiosis contained characteristic yellow, coral-like coagula and had a fibrotic surface containing sinus tract openings. Basidiobolomycosis was characterized by infrequent small yellow coagula and a yellow line of fungal invasion beneath an edematous surface. Lesions of conidiobolomycosis h...
Hooijberg EH, van den Hoven R, Tichy A, Schwendenwein I.A wide spectrum of laboratory tests is available to aid diagnosis and classification of equine inflammatory disease. Objective: To compare diagnostic efficacy and combined predictive capability of the myeloperoxidase index (MPXI), and plasma fibrinogen, iron and serum amyloid A (SAA) concentrations for the diagnosis of inflammation. Methods: Twenty-six hospitalized horses with systemic inflammation (SI), 114 with local inflammation (LI) and 61 healthy horses or those with noninflammatory disease (NI) were included. Methods: A retrospective study was performed; clinicopathologic data from horse...
Petrov R, MacDonald MH, Tesch AM, Benton HP.To investigate the effect of adenosine kinase inhibition on interleukin (IL)-1beta- and lipopolysaccharide (LPS)-induced cartilage damage. Methods: Articular cartilage was obtained from the metacarpophalangeal joints of 10 young adult horses. Following a stabilization period, weighed cartilage explants were exposed to IL-1beta (10 ng/ml) or LPS (50 microg/ml) to induce cartilage degradation. To test the potential protective effects of adenosine, these explants were simultaneously exposed to adenosine (100 microM), the adenosine kinase inhibitor 5'iodotubercidin (ITU, 1 microM) or to both adeno...
Go YY, Cook RF, Fulgêncio JQ, Campos JR, Henney P, Timoney PJ, Horohov DW, Balasuriya UB.In a recent study, we demonstrated that the virulent Bucyrus strain (VBS) of EAV could infect in vitro a small population of CD3(+) T lymphocytes from some but not all horses. Furthermore, we have shown that a common haplotype is associated with this in vitro CD3(+) T cell susceptibility/resistance phenotype to EAV infection. In this study, we investigated whether the differences in the susceptibility or resistance of CD3(+) T cells in vitro correlate with the outcome and severity of clinical signs in vivo. Thus, horses were divided into two groups based on their CD3(+) T cell susceptible or r...
Liu M, Liu T, Bordin A, Nerren J, Cohen N.Toll-like receptor 9 (TLR9) activation stimulates protective immune responses against intracellular pathogens by phagocytes, including neutrophils. This study examined TLR9-mediated neutrophil activation in neonatal foals. Unmethylated CpGs, ligands for TLR9, were used to stimulate equine neutrophils, either purified or in contact with other peripheral blood leukocytes. Rhodococcus equi was used as another stimulus in parallel. TLR9 mRNA was constitutively expressed at a similar level in purified equine neutrophils across different ages from birth to adulthood, and expression was not affected ...
Geor RJ.Epidemiologic studies indicate that most laminitis cases occur in horses and ponies kept at pasture, hence the term 'pasture-associated laminitis'. Clinical cases of laminitis most often occur under conditions that favor accumulation of rapidly fermentable nonstructural carbohydrates (fructans, simple sugars, or starches) in pasture, and animals with an equine metabolic syndrome (EMS) phenotype (insulin resistance, abnormal insulin dynamics, +/- obesity) seem to be at highest risk for developing the condition. Although the mechanisms linking consumption of pasture forage with development of la...
Tuppits U, Orro T, Einarsson S, Kask K, Kavak A.The aim of this study was to investigate the clinical relevance of measuring blood concentrations of serum amyloid A (SAA), haptoglobin (Hp) and fibrinogen (Fib) in horse reproductive management, and changes in response to artificial insemination (AI) with frozen-thawed semen. Standardbred mares (n=18) with different reproductive status (eight healthy mares in first postpartum oestrus, five healthy barren mares and five mares with endometritis) were inseminated with frozen-thawed semen. Endometritis was evaluated during oestrus by bacteriological culture, cytology and presence of ultrasonicall...
Jaworska J, Janowski T.Retained fetal membranes (RFM) is a prevalent postpartum disease in mares. During parturition, various proinflammatory cytokines are released in the placenta, which further facilitates uterine contractions, expulsion of the fetus and fetal membranes. We hypothesized that an altered inflammatory response in mares results in retained fetal membranes. Samples of the endometrium and the allantochorion were collected from 15 mares with RFM and from 29 control mares within 2 h of foal delivery. Next, the mRNA expression of IL-1β, IL-6 and TNFα proteins was analyzed by Real Time PCR and Western b...
Bryant CE, Ouellette A, Lohmann K, Vandenplas M, Moore JN, Maskell DJ, Farnfield BA.Sepsis and endotoxaemia are important causes of morbidity and mortality in humans. Research on sepsis focuses on rodent models most of which are poorly responsive to lipopolysaccharide (LPS), and thus do not mimic very well the high sensitivity of humans. Therefore, there is a need to develop more clinically relevant models. Horses suffer from a similar endotoxaemic syndrome to humans with high morbidity and mortality. LPS analogues that act as antagonists at Toll-like receptor 4 (TLR4) are being developed as novel treatments for endotoxaemia. Due to differences in recognition of ligands by TL...
Mustonen AM, Lehmonen N, Paakkonen T, Raekallio M, Käkelä R, Niemelä T, Mykkänen A, Sihvo SP, Nieminen P.Individual fatty acids (FAs) and their derivatives (lipid mediators) with pro-inflammatory or dual anti-inflammatory and pro-resolving properties have potential to influence the health of joint tissues. Osteoarthritis (OA) is an age-associated chronic joint disease that can be featured with altered FA composition in the synovial fluid (SF) of human patients. The counts and cargo of extracellular vesicles (EVs), membrane-bound particles released by synovial joint cells and transporting bioactive lipids, can also be modified by OA. The detailed FA signatures of SF and its EVs have remained unexp...
Ma J, Wang SS, Lin YZ, Liu HF, Liu Q, Wei HM, Wang XF, Wang YH, Du C, Kong XG, Zhou JH, Wang X.The Chinese attenuated equine infectious anemia virus (EIAV) vaccine has successfully protected millions of equine animals from EIA disease in China. Given that the induction of immune protection results from the interactions between viruses and hosts, a better understanding of the characteristics of vaccine strain infection and host responses would be useful for elucidating the mechanism of the induction of immune protection by the Chinese attenuated EIAV strain. In this study, we demonstrate in equine monocyte-derived macrophages (eMDM) that EIAVFDDV13, a Chinese attenuated EIAV strain, indu...
Henry MM, Moore JN.Increasing evidence has demonstrated the importance of monocyte procoagulant activity (PCA) in the pathogenesis of coagulopathies in a variety of diseases. Because endotoxin precipitated coagulopathies are common sequelae to intestinal ischemia/endotoxemia in the equine species, we investigated the ability of equine peripheral blood monocytes to express PCA. Monocytes isolated from five healthy adult horses were incubated in vitro with Escherichia coli endotoxin (10 micrograms), and the PCA was measured by the ability of cellular lysates to accelerate the clotting times of equine plasma in a m...
Fedorka CE, Scoggin KE, Boakari YL, Hoppe NE, Squires EL, Ball BA, Troedsson MHT.The deposition of semen into the uterus of the horse induces a transient innate immune response that lasts 24-36 h in the normal mare. There exists a subset of mares that are unable to resolve this inflammation in a timely manner, and are classified as susceptible to the disease of persistent breeding-induced endometritis (PBIE). Lactoferrin is a protein of interest as a potential therapeutic for this persistent inflammation due to its anti-inflammatory and bactericidal properties. The addition of human recombinant lactoferrin (hrLF) to the insemination dose was previously shown to suppress ...
Martin EM, Messenger KM, Sheats MK, Jones SL.Pro-inflammatory cytokines including tumor necrosis factor α (TNFα), IL-1β, IL-6, and IL-8 are potent immune mediators that exacerbate multiple equine diseases such as sepsis and laminitis. Unfortunately, safe and effective cytokine-targeting therapies are lacking in horses; therefore, novel mechanisms of inhibiting cytokine production are critically needed. One potential mechanism for inhibiting cytokine synthesis is elevation of intracellular cyclic AMP (cAMP). In human leukocytes, intracellular cAMP production is induced by activation of E-prostanoid (EP) receptors 2 and 4. These recepto...
Colbath AC, Dow SW, Hopkins LS, Phillips JN, McIlwraith CW, Goodrich LR.Allogeneic and autologous bone marrow-derived mesenchymal stem cells (BMDMSCs) have been administered in equine joints for their anti-inflammatory effects. However, allogeneic BMDMSC offer multiple clinical and practical advantages. Therefore, it is important to determine the relative effectiveness of allogeneic vs autologous BMDMSCs. Objective: The objective of the study was to compare the inflamed joint response to autologous vs allogeneic BMDMSCs injections, and to determine if either treatment generated an anti-inflammatory effect. Methods: Randomised controlled study. Methods: Bone marrow...
Fuchs B, Bondzio A, Wagner U, Schiller J.Alterations of the phospholipid (PL) compositions of body fluids are assumed to be indicative of inflammatory diseases, e.g. rheumatoid arthritis (RA). Recently, we have shown that particularly the phosphatidylcholine/lysophosphatidylcholine (PC/LPC) ratio determined in human synovial fluids (SF) and sera represents a reliable measure of the inflammatory state in RA patients. However, it is not yet clear to what extent the PC/LPC ratio is also affected by nutrition habits. In the present study, the PL and the corresponding acyl chain compositions of human body fluids (SF and serum of RA patien...
Horses affected by chronic piroplasmosis may develop poor performance and muscle atrophy. Here we investigate the pathological and immunopathological aspects of myopathy occurring in chronic equine piroplasmosis. The study included 16 horses serologically positive for equine piroplasms presenting with clinical signs and supporting serum biochemical evidence of a myopathy. Skeletal muscle was evaluated by histopathology, immunohistochemistry, indirect immunofluorescence, and molecular detection of piroplasms and inflammatory cytokines in skeletal muscle. Histologic lesions included muscle fiber...
Werners AH, Bull S, Vendrig JC, Smyth T, Bosch RR, Fink-Gremmels J, Bryant CE.The inter- and intra-species differences in the response to lipopolysaccharides (LPS) are well recognised in mammalian species. It has been hypothesized that these differences can be attributed to genetic polymorphisms in the components involved in LPS signal transduction. These components include the cluster of differentiation factor 14 (CD-14), a membrane bound protein on the surface of mononuclear cells that recognises LPS and a receptor complex consisting of Toll-like receptor-4 (TLR-4) and myeloid differentiation factor-2 (MD-2). Sequencing of these three proteins in humans and mice revea...
Ross-Jones TN, McIlwraith CW, Kisiday JD, Hess TM, Hansen DK, Black J.Dietary n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation has previously been shown to modify joint-related inflammation in several species, although information in the horse is lacking. We investigated whether dietary supplementation with n-3 LCPUFA would modify experimentally induced synovitis in horses. Twelve, skeletally mature, non-pregnant mares were randomly assigned to either a control diet (CONT) or an n-3 long-chain fatty acid-enriched treatment diet (N3FA) containing 40Â g/day of n-3 LCPUFA for 91Â days. Blood samples taken on days 0, 30, 60 and 90, and synovial flu...
Degroote RL, Hauck SM, Kremmer E, Amann B, Ueffing M, Deeg CA.The molecular mechanism which enables activated immune cells to cross the blood-retinal barrier in spontaneous autoimmune uveitis is yet to be unraveled. Equine recurrent uveitis is the only spontaneous animal model allowing us to investigate the autoimmune mediated transformation of leukocytes in the course of this sight threatening disease. Hypothesizing that peripheral blood immune cells change their protein expression pattern in spontaneous autoimmune uveitis, we used DIGE to detect proteins with altered abundance comparing peripheral immune cells of healthy and ERU diseased horses. Among ...
DeLuca L, Erb HN, Young JC, Perkins GA, Ainsworth DM.Chemokine expression in airway epithelium and bronchoalveolar lavage fluid (BALF) cells of horses with recurrent airway obstruction (RAO) is increased. Objective: For RAO-affected horses that are stabled and fed a pelleted ration, the addition of oral dexamethasone further improves pulmonary function and reduces inflammatory gene expression in pulmonary cells. Methods: Twelve RAO-affected horses. Methods: In a randomized cross-over experiment, the effect of feeding pellets in lieu of hay to stabled, RAO-affected horses was compared with the effect of feeding pellets and administering a 21-day ...
