Topic:Cytokines
Cytokines are small proteins that are important in cell signaling and are produced by various cell types in horses, particularly during immune responses. These molecules facilitate communication between cells and play a role in regulating inflammation, immune function, and hematopoiesis. In horses, cytokines are involved in numerous physiological and pathological processes, including infection, inflammation, and wound healing. Examples of cytokines studied in equine research include interleukins, interferons, and tumor necrosis factors. Their expression levels can change in response to disease states, making them potential biomarkers for assessing equine health and disease progression. This page compiles peer-reviewed research studies and scholarly articles that explore the role, regulation, and clinical implications of cytokines in equine health.
Immunohistochemical Expression of Neurokinin-A and Interleukin-8 in the Bronchial Epithelium of Horses with Severe Equine Asthma Syndrome during Asymptomatic, Exacerbation, and Remission Phase. Severe equine asthma (EA) syndrome is a chronic obstructive disease characterized by exaggerated contraction, inflammation, and structural alteration of the airways in adult horses, when exposed to airborne molds and particulate material. However, little is known about the relationship between the degree and type of inflammation on one hand, and the severity of the disease and the response to treatment on the other. Furthermore, to date, very few studies evaluate the diagnostic value of histology and immunohistochemical features of endoscopic biopsies on subjects with severe equine asthma. To ...
Investigation of synovial fluid lubricants and inflammatory cytokines in the horse: a comparison of recombinant equine interleukin 1 beta-induced synovitis and joint lavage models. Lameness is a debilitating condition in equine athletes that leads to more performance limitation and loss of use than any other medical condition. There are a limited number of non-terminal experimental models that can be used to study early inflammatory and synovial fluid biophysical changes that occur in the equine joint. Here, we compare the well-established carpal IL-1β-induced synovitis model to a tarsal intra-articular lavage model, focusing on serial changes in synovial fluid inflammatory cytokines/chemokines and the synovial fluid lubricating molecules lubricin/proteoglycan 4 and hya...
The effect of lower airway inflammation on inflammatory cytokine gene expression in bronchoalveolar lavage fluid and whole blood in racing Thoroughbreds. Immunological mechanisms involved in the pathogenesis of mild to moderate equine asthma (MEA) are not completely understood. There are limited data on bronchoalveolar lavage fluid (BALF) and blood inflammatory cytokine profiles in racehorses with MEA, and the effect of racing on inflammatory cytokines is unknown. Objective: We hypothesized that inflammatory cytokine gene expression in BALF and resting blood would be higher in racehorses with lower airway inflammation compared to healthy controls, and that gene expression in blood collected immediately post-race would be increased compared to r...
Equine cervical remodeling during placentitis and the prepartum period: a transcriptomic approach. Cervical remodeling is a critical component in both term and preterm labor in eutherian mammals. However, the molecular mechanisms underlying cervical remodeling remain poorly understood in the mare. The current study compared the transcriptome of the equine cervix (cervical mucosa (CM) and stroma (CS)) during placentitis (placentitis group, n = 5) and normal prepartum mares (prepartum group, n = 3) to normal pregnant mares (control group, n = 4). Transcriptome analysis identified differentially expressed genes (DEGs) during placentitis (5310 in CM and 907 in CS) and during the normal prepartu...
IgE-Binding Monocytes Have an Enhanced Ability to Produce IL-8 (CXCL8) in Animals with Naturally Occurring Allergy. IL-8 is a potent chemokine that recruits neutrophils and basophils to promote inflammation in many species. IL-8 is produced by many cell types, including monocytes. In this study, we report a novel role for IgE-binding monocytes, a rare peripheral immune cell type, to promote allergic inflammation through IL-8 production in a horse model of natural IgE-mediated allergy. We developed a mAb with confirmed specificity for both recombinant and native equine IL-8 for flow cytometric analysis. Equine IL-8 was produced by CD14/MHC class II/CD16 monocytes, including a subpopulation of IgE-binding mon...
Impact of Three Different Serum Sources on Functional Properties of Equine Mesenchymal Stromal Cells. Culture and expansion of equine mesenchymal stromal cells (MSCs) are routinely performed using fetal bovine serum (FBS) as a source of growth factors, nutrients, and extracellular matrix proteins. However, the desire to minimize introduction of xenogeneic bovine proteins or pathogens and to standardize cellular products intended for clinical application has driven evaluation of alternatives to FBS. Replacement of FBS in culture for several days before administration has been proposed to reduce antigenicity and potentially prolong survival after injection. However, the functional consequences o...
Aggrecan, IL-1β, IL-6, and TNF-α profiles in the Articular Cartilage of Miniature Horses with Chondrodysplastic Dwarfism. Dwarfism is a skeletal disorder that causes abnormal growth. In Miniature horses, dwarfism can occur as chondrodysplastic dwarfism, an autosomal recessive disorder associated with five mutations (D1, D2, D3*, D4 and c.6465A > T variant) in the aggrecan (ACAN) gene. The aim of this study was to evaluate the expression of aggrecan (at the gene and protein level) and specific cytokines (IL-1β, IL-6, and TNF-α) in the articular cartilage of Miniature horses with chondrodysplastic dwarfism (D4/c.6465A > T genotype). Metatarsal bone samples from eight dwarf Miniature horses were collected fo...
Intrauterine Blood Plasma Platelet-Therapy Mitigates Persistent Breeding-Induced Endometritis, Reduces Uterine Infections, and Improves Embryo Recovery in Mares. Microorganisms, including pathogenic or opportunistic bacteria and fungi, may gain access to the uterus during breeding, and infectious endometritis plays a major role in equine subfertility. This study aimed to assess the post-breeding inflammatory response, endometrial culture, and embryo recovery of mares susceptible to persistent breeding-induced endometritis (PBIE) treated with plasma-rich (PRP) or -poor (PPP) plasma. Mares (n = 12) susceptible to PBIE had three cycles randomly assigned to receive intrauterine infusions of lactate ringer solution (LRS, control), or autologous PRP or PPP p...
Toll-like receptor activation of equine mesenchymal stromal cells to enhance antibacterial activity and immunomodulatory cytokine secretion. To evaluate effects of Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor (TLR, NLR) ligand stimulation of equine mesenchymal stromal cells (MSCs) on antibacterial and immunomodulatory properties in vitro. Methods: Controlled laboratory study. Methods: Equine bone-marrow-derived MSCs (three horses). Methods: MSCs were stimulated with TLR (polyinosinic:polycytidylic acid [pIC] and lipopolysaccharide [LPS]) and NLR agonists (γ-d-Glu-mDAP [IE-DAP]) for 2 h, and plated at 1 × 105 cells/well 24 h. MSC-conditioned media (MSC-CM) were collected and assessed for antimicr...
A Critical Overview of the Use of Platelet-Rich Plasma in Equine Medicine Over the Last Decade. In the 1990s, the role of platelets in inflammation and tissue healing was finally recognized. Since then, the clinical use of platelet-derived products (hemocomponents), such as, platelet-rich plasma (PRP), markedly increased. The promise of a more economical option of a disease-modifying treatment led to the intensive and continuous research of PRP products and to its widespread clinical use. A number of protocols and commercial kits have been developed with the intention of creating a more practical and reliable option for clinical use in equine patients. Still, the direct comparison betwee...
Virulent African horse sickness virus serotype 4 interferes with the innate immune response in horse peripheral blood mononuclear cells in vitro. African horse sickness (AHS) is caused by African horse sickness virus (AHSV), a double stranded RNA (dsRNA) virus of the genus Orbivirus, family Reoviridae. For the development of new generation AHS vaccines or antiviral treatments, it is crucial to understand the host immune response against the virus and the immune evasion strategies the virus employs. To achieve this, the current study used transcriptome analysis of RNA sequences to characterize and compare the innate immune responses activated during the attenuated AHSV serotype 4 (attAHSV4) (in vivo) and the virulent AHSV4 (virAHSV4) (in...
Allogenic mesenchymal stem cell-conditioned medium does not affect sperm parameters and mitigates early endometrial inflammatory responses in mares. This study aimed to evaluate the effects of mesenchymal stem cell-conditioned medium (MSC-CM) on sperm parameters, intrauterine polymorphonuclear neutrophils (PMN), intrauterine fluid accumulation (IUF), and fertility in mares. In experiment 1, two ejaculates from ten stallions were extended to 50 million sperm/mL using a milk-based extender. Thereafter, 20 mL of extended semen was added of MSC-CM as follows: 0, 5, 10, 15, and 20 mL. Sperm kinetics and plasma membrane integrity were evaluated immediately after dilution (T0) and 2 h post-incubation at 37 °C (T2). In experiment 2, mares cha...
Equine Genital Squamous Cell Carcinoma Associated with EcPV2 Infection: RANKL Pathway Correlated to Inflammation and Wnt Signaling Activation. Equine genital squamous cell carcinomas (egSCCs) are among the most common equine tumors after sarcoids, severely impairing animal health and welfare. papillomavirus type 2 (EcPV2) infection is often related to these tumors. The aim of this study was to clarify the molecular mechanisms behind egSCCs associated with EcPV2 infection, investigating receptor activator of nuclear factor-kappa B ligand (RANKL) signaling in NF-kB pathway, together with the Wnt and IL17 signaling pathways. We analyzed the innate immune response through gene expression evaluation of key cytokines and transcription fac...
Dust exposure and pulmonary inflammation in Standardbred racehorses fed dry hay or haylage: A pilot study. Respirable dust exposure is linked to airway inflammation in racehorses. Feeding haylage may reduce dust exposure by 60-70%. The objective of this study was to compare dust exposure, airway cytology, and inflammatory cytokine concentrations between horses fed haylage or hay over 6 weeks while in training. Seven healthy Standardbred horses were randomly assigned to be fed alfalfa hay (n = 3) or grass-alfalfa mix haylage (n = 4) for six weeks while training on a treadmill. Dust exposure was measured gravimetrically at the breathing zone. Endotoxin and β-glucan concentrations in respirable dust ...
Use of quantitative real-time PCR to determine the local inflammatory response in the intestinal mucosa and muscularis of horses undergoing small intestinal resection. Studies in rodents and humans have demonstrated that intestinal manipulation or surgical trauma initiates an inflammatory response in the intestine which results in leucocyte recruitment to the muscularis externa causing smooth muscle dysfunction. Objective: To examine the intestinal inflammatory response in horses undergoing colic surgery by measuring relative differential gene expression in intestinal tissues harvested from surgical colic cases and control horses. Methods: Prospective case-control study. Methods: Mucosa and muscularis externa were harvested from healthy margins of resected s...
Evaluation of Treatment With Respiratory Gene Technology and Serum in a Group of Standard Bred Racehorses With Cytological Evidence of Mild Equine Asthma. Alternative treatment options to glucocorticoids for equine asthma is desirable due to withdrawal time. The objective was to evaluate if serum and Respiratory Gene Technology (RGT), a commercial kit to produce autologous conditioned serum, was effective in reducing bronchoalveolar lavage (BAL) neutrophils and mast cells in racehorses with cytological evidence of mild equine asthma . Thirty-six Standardbred trotters in active training were enrolled in this randomized clinical trial; a healthy control group (n=11), a RGT group (n=12) and a serum group (n=13). Endoscopy including tracheal wash (T...
A Comparative Review of Autologous Conditioned Serum and Autologous Protein Solution for Treatment of Osteoarthritis in Horses. Many alternative treatments aimed at modulating osteoarthritis (OA) progression have been developed in the past decades, including the use of cytokine inhibitors. IL-1β is considered one of the most impactful cytokines in OA disease and therefore, its blockage offers a promising approach for the modulation of OA. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring anti-inflammatory protein belonging to the IL-1 family that competes with IL-1β for occupancy of its receptors, without triggering the same downstream inflammatory response. Because of its natural anti-inflammatory ...
Alterations of Circulating Biomarkers During Late Term Pregnancy Complications in the Horse Part I: Cytokines. 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...
Investigation of innate immune function in adult and geriatric horses. In order to better understand the influence of age on innate immune function in horses, blood was collected from twelve adult horses (aged 10-16 years; mean: 13 years) and ten geriatric horses (aged 18-26 years; mean: 21.7 years) for analysis of plasma myeloperoxidase, complete blood counts, and cytokine and receptor expression in response to in vitro stimulation with heat-inactivated Rhodococcus equi, heat-inactivated Escherichia coli, and PMA/ionomycin. Gene expression was measured using RT-PCR for IFNγ, IL-1β, IL-6, IL-8, IL-10, IL-12α, IL-13, IL-17α, TLR2, TLR4, and TNFα. Endocrine fu...
Effects of continuous passage on the immunomodulatory properties of equine bone marrow-derived mesenchymal stem cells in vitro. The immunomodulatory properties of mesenchymal stem cells (MSCs) have been studied extensively due to their increasing clinical application for tissue regeneration and repair following culture expansion. We have studied the effect of continuous passage on the immunomodulatory capacity of equine bone marrow-derived MSCs (BM-MSCs). Equine BM-MSCs were isolated and culture expanded to passage three, six, and nine (P3, P6, P9). Immunomodulatory properties of each passage were assessed using a T cell proliferation assay and cytokine synthesis following stimulation with interferon gamma (IFN-γ). Re...
Evidence for anti-inflammatory effects of firocoxib administered to mares with experimentally induced placentitis. Minimal evidence exists supporting therapeutic selections for equine placentitis. The goal of this study was to characterize the anti-inflammatory effects of firocoxib when administered to mares with placentitis. Mares (gestation D270-300) were assigned to: INFECT (n = 6; placentitis, no treatment), FIRO (n = 6; placentitis, firocoxib, 0.1 mg/kg, PO, daily), and NORM (n = 6; no infection/treatment). Allantoic fluid (8 hours, 24 hours, birth) and amniotic fluid (birth) were collected from mares after infection. Concentrations of IL-1β, IL-6, TNF-α, IL-10, PGF , and PGE in fluids were...
Differential gene expression and Ingenuity Pathway Analysis of bronchoalveolar lavage cells from horses with mild/moderate neutrophilic or mastocytic inflammation on BAL cytology. Mild to moderate equine asthma syndrome (mEAS) affects horses of all ages and breeds. To date, the etiology and pathophysiology of mEAS are active areas of research, and it remains incompletely understood whether mEAS horses with different immune cell 'signatures' on BAL cytology represent different phenotypes, distinct pathobiological mechanisms (endotypes), varied environmental conditions, disease severity, genetic predispositions, or all of the above. In this descriptive study, we compared gene expression data from BAL cells isolated from horses with normal BALF cytology (n = 5), to those i...
TGF-β2 Reduces the Cell-Mediated Immunogenicity of Equine MHC-Mismatched Bone Marrow-Derived Mesenchymal Stem Cells Without Altering Immunomodulatory Properties. Allogeneic mesenchymal stem cells (MSCs) are a promising cell therapy for treating numerous diseases, but major histocompatibility complex (MHC)-mismatched MSCs can be rejected by the recipient's immune system. Pre-treating MSCs with transforming growth factor-β2 (TGF-β2) to downregulate surface expression of MHC molecules may enhance the ability of allogeneic MSCs to evade immune responses. We used lymphocyte proliferation assays and ELISAs to analyze the immunomodulatory potential of TGF-β2-treated equine bone marrow-derived MSCs. T cell activation and cytotoxicity assays were then used t...
Rare Case of Spinal Neurosarcoidosis with Concomitant Epidural Lipomatosis. 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...
Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia. 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...
Intrauterine infusion of killed semen adversely affects uterine blood flow and endometrial gene expression of inflammatory cytokines in mares susceptible to persistent breeding-induced endometritis. Persistent breeding-induced endometritis (PBIE) is a leading cause of infertility in mares. The objective of the study was to assess genital perfusion and endometrial gene expression of inflammatory cytokines in mares classified as susceptible (n = 5) or resistant (n = 5) to PBIE. Ten mares were examined daily during estrus until 6 d after hCG-induced ovulation for two estrous cycles. Twenty-four hours after application of 1500 IU hCG, 4 mL of killed (by repeated freezing in liquid nitrogen and thawing at 50 °C) deep-frozen semen or sterile saline was instilled into the uterine body an...
Marine Collagen Hydrolysates Downregulate the Synthesis of Pro-Catabolic and Pro-Inflammatory Markers of Osteoarthritis and Favor Collagen Production and Metabolic Activity in Equine Articular Chondrocyte Organoids. Articular cartilage experiences mechanical constraints leading to chondral defects that inevitably evolve into osteoarthritis (OA), because cartilage has poor intrinsic repair capacity. Although OA is an incurable degenerative disease, several dietary supplements may help improve OA outcomes. In this study, we investigated the effects of Dielen® hydrolyzed fish collagens from skin (Promerim®30 and Promerim®60) and cartilage (Promerim®40) to analyze the phenotype and metabolism of equine articular chondrocytes (eACs) cultured as organoids. Here, our findings demonstrated the absence of cyto...
MMP-9 Concentration in Peritoneal Fluid Is a Valuable Biomarker Associated with Endotoxemia in Equine Colic. The purpose of the study was to compare the results of sepsis scoring (clinical examination and clinical pathology) to the concentrations of matrix-metalloproteinases (MMPs) -2, -8, and -9; tissue-inhibitor of metalloproteinases (TIMPs) -1 and -2; and inflammatory chemokines interleukin (IL) 1β and tumor-necrosis-factor-alpha (TNF-α) in plasma and peritoneal fluid of equine colic patients. A modified sepsis scoring including general condition, heart and respiratory rate, rectal temperature, mucous membranes, white blood cell count (WBC), and ionized calcium was applied in 47 horses presented...
Cross-matching of allogeneic mesenchymal stromal cells eliminates recipient immune targeting. Allogeneic mesenchymal stromal cells (MSCs) have been used clinically for decades, without cross-matching, on the assumption that they are immune-privileged. In the equine model, we demonstrate innate and adaptive immune responses after repeated intra-articular injection with major histocompatibility complex (MHC) mismatched allogeneic MSCs, but not MHC matched allogeneic or autologous MSCs. We document increased peri-articular edema and synovial effusion, increased synovial cytokine and chemokine concentrations, and development of donor-specific antibodies in mismatched recipients compared wi...
Interleukin-17A pathway target genes are upregulated in Equus caballus supporting limb laminitis. 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...