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Topic:Interleukins
Interleukins are a group of cytokines, which are signaling proteins, that are produced by various cells in the horse's body, including immune cells. They are involved in the regulation of immune responses, inflammation, and hematopoiesis. Interleukins facilitate communication between cells during immune responses and can influence the behavior of other cells. In horses, interleukins such as IL-1, IL-6, and IL-10 have been studied for their roles in inflammatory processes and immune regulation. Their expression and regulation are important for understanding immune function and disease pathogenesis in equine health. This page compiles peer-reviewed research studies and scholarly articles that explore the roles, mechanisms, and clinical implications of interleukins in horses.
Matrix metalloproteinase-2 and -9 are activated in joint diseases. A study was performed to identify the activation status of the gelatinase MMPs, MMP-2 and -9, in both normal and diseased equine articular tissues. In addition, the production and activation status of equine MMP-2 and -9 by equine articular cells and tissues in response to increasing IL-1beta concentrations was assessed. The study was performed to test the hypothesis that activation of MMPs is a fundamental step in the pathogenesis of joint diseases; and that this activation is mediated by the cytokine IL-1. Using purified equine MMP-2 and -9, the molecular weights of the zymogen and activated...
Plasma and urine nitric oxide concentrations in horses given below a low dose of endotoxin. To quantify plasma and urine nitric oxide (NO) concentrations before and after low-dose endotoxin infusion in horses. Methods: 11 healthy adult female horses. Procedure-Eight horses were given endotoxin (35 ng/kg of body weight,i.v.) over 30 minutes. Three sentinel horses received an equivalent volume of saline (0.9% NaCl) solution over the same time. Clinical signs of disease and hemodynamic variables were recorded, and urine and plasma samples were obtained to measure NO concentrations prior to endotoxin infusion (t = 0) and every hour until postinfusion hour (PIH) 6, then every 2 hours unti...
Nitric oxide synthase activity in healthy and interleukin 1beta-exposed equine synovial membrane. To quantitate nitric oxide synthase (NOS) activity in healthy and interleukin 1beta (IL-1beta)-exposed equine synovial membrane. Methods: 6 healthy horses, 2 to 8 years old. Methods: Recombinant human IL-1beta (0.35 ng/kg of body weight) was injected intra-articularly into 1 metacarpophalangeal joint of each horse. The contralateral joint served as an unexposed control. All horses were euthanatized 6 hours after injection of IL-1beta, and synovial membrane specimens were assayed for NOS activity by measuring conversion of arginine to citrulline. Severity of inflammation was semiquantitated by ...
Characterisation of equine T helper cells: demonstration of Th1- and Th2-like cells in long-term equine T-cell cultures. The aim of this study was to characterise CD4+T-cells in equines, as these cells are pivotal in establishing immune responses or regulating established ones. Peripheral blood mononuclear cells from a pony immunised with ovalbumin were cultured in vitro in the presence of the specific antigen and autologous antigen presenting cells. During the antigen starvation phase, cells were maintained on recombinant equine IL-2. After 35 days of culture, most of the cells were CD4+, CD8-and sIg-. Cells proliferated specifically in the presence of antigen, as tested on day 42 of culture. These cells were a...
Increased interleukin-6 activity in the serum of ponies acutely infected with equine infectious anaemia virus. Seven ponies were infected with the virulent wild-type Wyoming strain of equine infectious anaemia virus (EIAV). Infection status was monitored by serum reverse transcriptase activity, rectal temperature, and complete blood count. Preinfection serum and serum obtained during the initial febrile episode following infection were assayed for interleukin 6 (IL-6) activity. Postinfection IL-6 activity was significantly increased as compared to preinfection values. The magnitude of increase in IL-6 was positively correlated with reverse transcriptase activity (an indirect measure of viraemia) but wa...
Quantitation of equine cytokine mRNA expression by reverse transcription-competitive polymerase chain reaction. A reverse transcription-competitive polymerase chain reaction (RT-cPCR) method was developed to quantitate equine interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 p35, IL-12 p40, interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha), and beta-actin mRNA expression. Using primers based on equine-specific sequences, these cytokines could be detected in concanavalin A-stimulated peripheral blood mononuclear cells. The specificity of the amplified product was confirmed by sequencing. For each cytokine, the assay was made quantitative by generating competitor ...
Effect of a conjugate of polymyxin B-dextran 70 in horses with experimentally induced endotoxemia. To determine the efficacy of polymyxin B-dextran 70 (PBD) for treatment of endotoxemic horses. Methods: 15 horses during study 1 and 6 horses during study 2. Methods: 3 groups were used in study 1. Horses in groups 1 and 2 were given 30 ng of lipopolysaccharide (LPS)/kg of body weight, IV, over 60 minutes. Horses in group 3 were given saline (0.9% NaCl) solution. Beginning 15 minutes before LPS infusion and continuing for 75 minutes, horses in groups 1 and 3 were given PBD, IV. Horses in group 2 were given dextran 70. Blood samples were obtained for hemograms and determination of cytokine, lac...
Effects of R and S enantiomers and a racemic mixture of carprofen on the production and release of proteoglycan and prostaglandin E2 from equine chondrocytes and cartilage explants. To examine effects of carprofen (enantiomers and a racemic mixture) on the metabolism of equine chondrocytes. Methods: Cartilage from clinically normal horses. Methods: Effects of carprofen on proteoglycan neosynthesis, glycosaminoglycan (GAG) release and prostaglandin (PG) E2 production by unstimulated chondrocyte monolayers and cartilage explants were examined, as were similar variables in monolayers and explants exposed to carprofen and recombinant human interleukin 1beta (IL-1). Carprofen (enantiomers and racemic mixture) was used alone or along with IL-1 on monolayers and explant cultures...
In vitro reactivation of latent equid herpesvirus-1 from CD5+/CD8+ leukocytes indirectly by IL-2 or chorionic gonadotrophin. IL-2 and equine chorionic gonadotrophin (eCG) initiated reactivation of equid herpesvirus-1 (EHV-1) from venous lymphocytes at a frequency of 1/10(-5). Indirect immunofluorescence showed that > 80% of virus-positive leukocytes were CD5+/CD8+ with the remaining 20% being CD5+/CD8-/CD4-. Cocultivation demonstrated that the reactivated virus was infectious. In addition, virus was reactivated in vitro from leukocytes of > 70% of horses by the mitogens phytohaemagglutinin (PHA) and pokeweed mitogen (PWM). Transfer of supernatants showed that IL-2 and eCG acted indirectly by causing the releas...
The role of neutrophil chemotactic cytokines in the pathogenesis of equine chronic obstructive pulmonary disease (COPD). Chronic obstructive pulmonary disease (COPD) is defined as a chronic obstructive inflammatory disease affecting the small airways associated with hay dust exposure (Lowell, F.C., 1964. Observation on heaves. An asthma like syndrome in the horse, J. Allergy 35, 322-330). The disease corresponds histopathologically to a chronic bronchiolitis (Gerber, H., 1973. Chronic pulmonary disease in the horse, Equine Vet. J. 5, 26-33; Winder, N.C., Grünig, G., Hermann, M., Howald, B., von Fellenberg, R., 1989. Comparison of respiratory secretion cytology and pulmonary histology in horses, J. Vet. Med., A3...
Pathogenesis of Babesia caballi infection in experimental horses. The present study was designed to investigate the role of cytokines in the pathogenesis of Babesia caballi in experimentally infected horses. The expression of cytokine mRNA was determined by using reverse transcription-polymerase chain reaction in two B. caballi-infected horses for 2 weeks after the infection. In one horse, there was up-regulation of interferon-gamma, tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 mRNAs, while in the second horse, expression of only TNF-alpha mRNA was up-regulated. No change was observed in interleukin-4 mRNA in both of the horses. To know the rela...
Interaction of transforming growth factor-beta-1 with alpha-2-macroglobulin from normal and inflamed equine joints. Binding between equine plasma alpha-2-macroglobulin (alpha 2M) and several cytokines known to participate in inflammatory reactions in other species was initially examined. Plasma was obtained from 5 horses with various abnormalities. Samples, both untreated and after reaction with methylamine, were incubated with exogenous, radiolabeled, porcine-derived transforming growth factor-beta-1 (125I-TGF-beta 1), recombinant human interleukin-1-beta (125I-IL-1 beta), and recombinant human tumor necrosis factor-alpha (125I-rhTNF-alpha). They were then subjected to nondenaturing polyacrylamide gel elec...
Local hemodynamics, permeability, and oxygen metabolism during acute inflammation of innervated or denervated isolated equine joints. To determine oxygen metabolism, permeability, and blood flow in isolated joints in response to interleukin 1beta (IL-1beta) and contribution of innervation. Methods: One metacarpophalangeal (MCP) joint of 24 adult horses. Methods: The MCP joint was isolated for 6 hours in a pump-perfused, auto-oxygenated, innervated or denervated preparation. Isolated joints were assigned to the following 4 groups: control, control-denervated, inflamed, and inflamed-denervated, and inflammation was induced by intra-articular injection of IL-1beta. Circuit arterial and venous pressures, flows, and blood gas ten...
Cloning of equine interleukin 1 receptor antagonist and determination of its full-length cDNA sequence. To clone equine interleukin 1 receptor antagonist (IL-1ra) and determine its full-length cDNA sequence. Methods: A cDNA library derived from lipopolysaccharide-stimulated equine monocytes was screened by means of plaque hybridization to radiolabeled equine IL-1ra DNA probes generated by means of the polymerase chain reaction. The cDNA nucleotide sequence for equine IL-1ra was determined by use of the dideoxy chain termination technique, analyzed by use of computer software for sequence characteristics, and compared with sequences reported for IL-1ra of other species. Results: The cDNA of equin...
Effect of synovial membrane infection in vitro on equine synoviocytes and chondrocytes. To determine the functional response of synovium to infection, and the influence of infected synovium on articular cartilage metabolism. Methods: Synovium and articular cartilage explants from the midcarpal and tarsocrural joints of adult horses. Methods: For experiment 1, synovium explants were incubated as follows: control--incubation in standard medium, infected (I)--incubation with Staphylococcus aureus, and infected-filtered (IF)--incubation with medium collected from the infected group and filtered (0.22-micron filter). Daily collected medium was assayed for interleukin 1 beta (IL-1 beta...
Hemostatic and fibrinolytic indices in neonatal foals with presumed septicemia. Thirteen coagulation tests evaluating hemostatic and fibrinolytic indices and serum cytokine and plasma endotoxin concentrations were obtained in 34 foals with a positive sepsis score (septic group) and 46 age-matched healthy foals. Compared to healthy foals, the prothrombin, activated partial thromboplastin, and whole blood recalcification times were significantly longer in septic foals. The fibrinogen and fibrin degradation products concentrations, percent plasminogen, alpha-2 antiplasmin, and plasminogen activator inhibitor activities, and tumor necrosis factor and interleukin-6 activities ...
Cell trafficking, mediator release, and articular metabolism in acute inflammation of innervated or denervated isolated equine joints. To describe the acute cellular response, inflammatory mediator release, and effect on chondrocyte metabolism of interleukin 1 beta (IL-1 beta) in isolated innervated or denervated equine metacarpophalangeal joints. Methods: One metacarpophalangeal joint of 24 adult horses. Methods: The metacarpophalangeal joint was isolated for 6 hours in a pump-perfused, auto-oxygenated, innervated or denervated metacarpophalangeal joint preparation. Isolated joints were assigned to 4 groups: control, control-denervated, inflamed, and inflamed-denervated, and inflammation was induced by intra-articular inject...
Molecular cloning and cartilage gene expression of equine stromelysin 1 (matrix metalloproteinase 3). To clone and determine molecular structure of equine stromelysin 1 (matrix metalloproteinase 3) and examine stromelysin expression in articular cartilage. SAMPLES AND PROCEDURE: Total RNA was harvested from equine arthritic cartilage specimens and was used for reverse transcription and polymerase chain reaction amplification to develop overlapping complementary DNA (cDNA) clones. Four cDNA sequences were ligated into plasmid (pGEM3Z) constructs and subcloned into bacterial expression vectors, and sequence was determined by automated dye terminator sequencing. Stromelysin mRNA expression was as...
Infection of bone marrow macrophages by equine infectious anemia virus. To characterize infection of bone marrow-derived macrophages (BMDM) with equine infectious anemia virus (EIAV) by determining virus production, effects on viability, and induction of cytokines. Methods: BMDM obtained from bone marrow of 6 clinically normal adult horses. Methods: BMDM were infected with EIAV at a multiplicity of infection of 8. Cell viability, percentage of cells with detectable viral protein, reverse transcriptase activity, and concentrations of infective virus (focus-forming units/ml), interleukin 6, and tumor necrosis factor-alpha were measured in culture supernatant samples...
Effects of pentoxifylline infusion on response of horses to in vivo challenge exposure with endotoxin. To evaluate the effect of pentoxifylline on response of horses to in vivo challenge exposure with endotoxin. Methods: 24 healthy horses in 3 treatment groups: pentoxifylline, endotoxin, or endotoxin and pentoxifylline. Methods: Horses of the pentoxifylline group were given a bolus of pentoxifylline (7.5 mg/kg of body weight, i.v.), followed by an infusion (3 mg/kg/h) over 3 hours, and those of the endotoxin group were given 20 ng of endotoxin/kg i.v. over 30 minutes. Those of the combination group were given both of the aforementioned compounds; pentoxifylline was administered immediately afte...
IL-1 beta induces the degradation of equine articular cartilage by a mechanism that is not mediated by nitric oxide. Proteoglycan degradation was induced in young equine articular cartilage explants cultured for eight days in the presence of 50 ng/ml recombinant human interleukin-1 beta. Degradation was initiated after 6 hours of exposure to the cytokine. This was accompanied by an induction of nitric oxide synthesis and a decrease in the incorporation of [36S]sulphate into the glycosaminoglycan chains of proteoglycans. The addition of 1mM N-iminoethyl-L-ornithine (an inhibitor of nitric oxide synthase) to the explant cultures in the presence of rhIL-1 beta suppressed the synthesis of NO and restored proteog...
Cloning of equine type II procollagen and the modulation of its expression in cultured equine articular chondrocytes. The complete nucleotide sequence of equine type II procollagen has not been previously reported, and equine-specific probes have not been available. We report the complete sequence and discuss the molecular characteristics of equine type II procollagen mRNA which was cloned from a cDNA library prepared from mRNA isolated from equine articular chondrocytes. The coding sequence (4257 bp) was 92.4% homologous to the cDNA of the human sequence, and the propeptide was 97% identical to the human sequence. We demonstrated that when equine chondrocytes are grown in phenotypically-maintained cultures, ...
Cytokine RNA expression in an equine CD4+ subset differentiated by expression of a novel 46-kDa surface protein. Two monoclonal antibodies (MAb), HB65A (IgG2a) and HB86A (IgGI), recognize a unique cell surface molecule on equine T-lymphocytes. The molecule, designated EqWC4, identified by these MAbs is present on a subpopulation of CD4+ equine lymphocytes (6.3-10.2% of Arabian lymphocytes CD4+ WC4+) and a smaller population of CD8+ lymphocytes (0.5% to 1.2% of Arabian lymphocytes CD8+ WC4+). EqWC4 is absent from B-lymphocytes, granulocytes, and macrophages. Both MAbs bound to a 46-kDa protein following immunoprecipitation reactions with lysates of surface labeled thymocytes. Immunoaffinity purification u...
Molecular cloning and functional expression of equine interleukin-1 receptor antagonist. Equine interleukin-1 receptor antagonist (IL-1ra) was molecularly cloned to establish a basis for cytokine therapy of acute and chronic inflammatory diseases in the horse. cDNA clones encoding the whole coding sequence of equine IL-1ra were isolated from equine peripheral blood mononuclear cells (PBMC) that had been stimulated with lipopolysaccharide (LPS). The equine IL-1ra cDNA obtained in this study contained an open reading frame encoding 177 amino acid residues. The predicted amino acid sequence of equine IL-1ra shared 75.7, 75.3 and 76.3% similarity with sequences of human, murine and ra...
Melatonin protects mice infected with Venezuelan equine encephalomyelitis virus. We investigated whether the administration of melatonin (MLT) reduces the death rate and evolution of the disease in mice infected with Venezuelan equine encephalomyelitis (VEE) virus. Our results show that, MLT protects mice infected with the virus. The mortality rate was reduced from 100% to 16% merely by increasing the dose from 0 to 1000 micrograms/MLT per kg body weight MLT significantly postponed the onset of the disease and death by several days. In surviving mice very high titres of VEE virus IgM antibodies were found seven weeks after virus inoculation. MLT significantly reduced VEE v...
Insulin-like growth factor 1 and corticosteroid modulation of chondrocyte metabolic and mitogenic activities in interleukin 1-conditioned equine cartilage. To evaluate potential stimulatory or matrix-sparing effects of insulin-like growth factor 1 (IGF-1), alone or in combination with a corticosteroid, in an interleukin 1 (IL-1)-induced model of cartilage degradation. Methods: Cartilage from the weightbearing surfaces of trochlea and condyles of clinically normal 2-year-old male horses. Methods: Triamcinolone acetonide and IGF-1 effects were evaluated by assessing: matrix responses by sulfated glycosaminoglycan (GAG) assay and [35S]sulfated GAG synthesis; collagen content by hydroxyproline assay; and mitogenic response by [3H]thymidine incorporat...
In-vitro modulation of plasminogen activator activity, prostaglandin E and nitric oxide production by interleukin-1 in pregnant mare serum gonadotrophin-primed theca-interstitial cells. To examine the participation of the theca-interstitial (TI) compartment in cytokine modulation of ovarian function, the effects of interleukin-1beta (IL-1) on plasminogen activator (PA) activity and on prostaglandin E (PGE) and nitric oxide (NO) production were examined in cultures of pregnant mare serum gonadotrophin (PMSG)-primed rat TI cells. Exposure to IL-1 (10 ng/ml) resulted in a 25% reduction (P < 0.001) in PA activity, concurrent with a 4.6-fold increase in the ability of the corresponding conditioned media to inhibit exogenous urokinase activity. IL-1 also produced a 4.7-fold incr...
Nitric oxide production by equine articular cells in vitro. Recent research in several species has suggested nitric oxide (NO) as a mediator of articular cartilage damage and an inhibitor of cartilage matrix neosynthesis. This study investigated NO production by cultured equine articular chondrocytes in response to 2 arthritogenic molecules, namely lipopolysaccharide (LPS) and interleukin-1 beta (IL-1 beta), and compared NO production by cultured equine synoviocytes stimulated with LPS. Synoviocytes exhibited a low basal level of NO synthesis (measured as nitrite, a NO metabolite) that was neither significantly increased nor decreased by exposure to LP...
Modulation of matrix metalloprotease 13 (collagenase 3) gene expression in equine chondrocytes by interleukin 1 and corticosteroids. To determine whether matrix metalloprotease 13 (MMP-13; collagenase 3) is produced by equine chondrocytes and to investigate modulation of its expression by recombinant human interleukin 1 beta (rhIL-1 beta) and corticosteroids. Methods: Equine chondrocytes in monolayer culture were stimulated with rhIL-1 beta. Total RNA was extracted, purified, and reverse transcribed into DNA. Using appropriate primers, a putative MMP-13 fragment was amplified by polymerase chain reaction, and cloned into a bacterial vector. The resultant fragment was purified and sequenced, then was used to prepare a digoxi...
Effects of flunixin, tolfenamic acid, R(-) and S(+) ketoprofen on the response of equine synoviocytes to lipopolysaccharide stimulation. The objective of this study was to analyse the effects of 4 nonsteroidal anti-inflammatory drugs (NSAIDs) on the production of beta-glucuronidase (beta-glu), tumour necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interleukin-1 (IL-1) and prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-stimulated equine synoviocytes. The agents studied were flunixin, tolfenamic acid, S(+)ketoprofen (KTP) and R(-)ketoprofen. LPS-induced release of beta-glu from synoviocytes was inhibited in a concentration dependent manner by all 4 compounds, tolfenamic acid being the most potent. Of the 2 KTP enant...
