Systemic Inflammation: What the Research Says
Evidence from 21 peer-reviewed studies
What Professionals Should Know
- •Doramapimod shows promise as a potential anti-inflammatory therapy for systemic inflammatory response in horses, though clinical efficacy in natural disease requires further investigation
- •The drug appears safe for IV administration and may help modulate excessive inflammatory responses by reducing pro-inflammatory cytokine production
- •This is preliminary evidence; clinical trials in naturally occurring disease are needed before recommending doramapimod as standard treatment for equine systemic inflammation
- •Meloxicam may be a safer alternative to flunixin meglumine for managing pain during systemic inflammatory conditions, particularly given its reduced GI toxicity profile
- •Pre-treating with meloxicam 60 minutes before an inflammatory challenge provides measurable pain reduction, suggesting potential prophylactic value in high-risk situations
- •This COX-2 selective approach offers a pharmacological option that addresses pain without suppressing the broader inflammatory response, which may be beneficial for recovery
- •Measuring specific leukocyte gene expression patterns could help clinicians differentiate between localized joint inflammation and systemic inflammatory responses in horses with similar clinical signs
- •Understanding the molecular signature of local versus systemic inflammation may improve diagnostic accuracy and guide earlier intervention decisions for conditions like synovitis or sepsis
- •Blood-based molecular markers could serve as objective tools to monitor disease progression and treatment response in inflammatory conditions
- •When weight gain is necessary (rehabilitation, sales prep), consider fat and fibre-based supplements over high-starch concentrates to minimise systemic inflammation and associated metabolic stress
- •Body condition score alone does not predict inflammatory state—diet quality matters; two horses at the same BCS may have different inflammatory profiles depending on what they're eating
- •High-NSC commercial concentrates may trigger metabolic inflammation in Thoroughbreds even before obesity develops, suggesting diet choice is important for metabolic health prevention
- •Request ESR testing at admission for colic cases as part of rapid prognostic assessment—low values may indicate higher risk of deterioration or death
- •Use ESR alongside other biomarkers to strengthen early clinical decision-making about treatment intensity and referral urgency
- •For surgical colics, repeat ESR at 24 hours post-op to monitor systemic inflammation trajectory and recovery prognosis
- •Machine learning-based prognostic tools using readily available clinical data plus viscoelastic testing may help identify horses with colic at highest mortality risk earlier in treatment
- •L-lactate concentration should remain a critical component of prognostic assessment in acute colic cases, as it provides strong predictive value across multiple model types
- •Viscoelastic coagulation testing adds predictive value when combined with clinical variables in ML models, but coagulopathy diagnosis alone is insufficient for survival prediction and should not be used as a standalone prognostic indicator
- •Arthrospira-based feed additive enriched with chromium, magnesium, and manganese may help manage insulin resistance and weight in metabolically affected horses as part of a comprehensive EMS management program
- •This supplement shows promise for reducing inflammatory markers and improving body condition in horses with EMS, potentially reducing reliance on other management interventions
- •Consider this as a complementary strategy alongside diet management and exercise for horses struggling with metabolic syndrome
- •Consider gastrointestinal stress when horses are subjected to combined transport and exercise stressors; monitor for signs of systemic inflammation
- •Management protocols should account for the cumulative effect of transport stress and exercise on gut health and immune function
- •Horses recovering from or prone to gut-related issues may require modified exercise schedules around transport events
- •D-dimer can be used as a prognostic marker in critically ill horses, but practitioners should understand that current assays are human-derived and their reliability in horses varies
- •Elevation of d-dimer correlates with systemic inflammation and thrombotic disease severity; clinicians should consider which assay is being used when interpreting results
- •Until equine-specific d-dimer assays are available, understanding the limitations and comparative performance of human assays is essential for appropriate clinical interpretation in horses with colic and systemic disease
- •Genetic testing based on these four candidate regions may eventually help identify horses predisposed to EMS before clinical signs develop, enabling earlier preventative management
- •Metabolomic biomarkers identified in this study could lead to faster, more accurate diagnostic tools than current insulin assays, improving the timeliness of EMS diagnosis and treatment
- •Understanding the genetic basis of EMS susceptibility may inform selective breeding decisions to reduce the prevalence of metabolic syndrome in at-risk populations like Arabians
- •Endotoxemia may not be the primary driver of laminar tissue inflammation in laminitis—focus on controlling dietary carbohydrate intake and managing gastric dysbiosis in at-risk horses
- •Laminitis development involves local laminar tissue responses beyond systemic inflammation, suggesting that therapies targeting only circulating endotoxins may be insufficient
- •In hospitalized horses with gastrointestinal disease, consider that dietary management and carbohydrate fermentation may pose greater laminitis risk than endotoxin translocation alone
- •Early differentiation between idiopathic peritonitis and NSII is critical—idiopathic cases respond to medical management while NSII requires surgical intervention and carries poor prognosis
- •Monitor clinical and laboratory parameters carefully in peritonitis cases to guide treatment decisions and provide accurate prognostic counselling to owners
- •Consider S. vulgaris as a potential underlying cause of NSII in horses, particularly in regions with documented increased prevalence; selective deworming protocols may need reassessment
- •PB-MSC therapy shows promise as a potential treatment for sepsis in horses but evidence of clinical benefit is not yet established
- •This therapy appears safe when administered intravenously, making it a candidate for further clinical investigation
- •Additional research is needed to determine whether PB-MSC treatment would improve outcomes in septic horses compared to standard care
- •Spirulina platensis supplementation may offer a complementary dietary strategy to support management of EMS horses by improving insulin sensitivity and reducing systemic inflammation
- •Weight loss coupled with improved insulin sensitivity suggests potential benefit as an adjunctive therapy alongside conventional EMS management (dietary restriction, exercise, medications)
- •Results are preliminary in vivo findings; further controlled clinical trials with defined sample sizes and control groups are needed before recommending widespread use in practice
- •Saliva sampling offers a non-invasive method to monitor systemic inflammation in horses, potentially reducing stress and handling compared to blood sampling
- •Presence of acute phase proteins in saliva may allow veterinarians to screen for systemic inflammatory disease using a simple, animal-friendly collection method
- •Further validation is needed before salivary biomarkers can be reliably used as a diagnostic tool in equine clinical practice
- •Red maple leaf toxicosis causes severe hemolytic anemia with high mortality (59%); monitor for signs of poisoning if wilted leaves are accessible to horses
- •Avoid corticosteroid administration in red maple toxicosis cases, as it significantly worsens prognosis
- •Development of fever during hospitalization is a favorable prognostic indicator; initial blood parameters alone cannot predict survival outcomes
- •Understanding NETosis mechanisms may reveal new therapeutic targets to modulate excessive immunothrombosis in critical conditions affecting companion animals.
- •Measuring cell-free DNA and extracellular trap markers could become clinically useful diagnostic tools for assessing systemic inflammation severity in horses, dogs, and cats.
- •Clinicians should recognize that while NETosis aids innate immunity, excessive trap formation in damaged blood vessels can be harmful and may warrant anti-inflammatory or NET-inhibiting interventions.
- •Insulin at 3 IU/kg may offer an alternative anti-inflammatory approach to NSAIDs like flunixin in donkeys experiencing systemic inflammation, potentially useful when NSAID use is contraindicated
- •Dosing matters: the higher insulin dose (3 IU/kg) was necessary for therapeutic anti-inflammatory effect; lower doses may be insufficient
- •This represents a novel application of insulin outside its traditional glucose-regulatory role; further clinical validation in naturally occurring inflammatory conditions would be needed before routine practice adoption
- •The POC test can be used for SAA measurement in equine serum/plasma, but whole blood results are not interchangeable and should not be compared directly with serum/plasma or reference laboratory values
- •If serial SAA monitoring is needed, use samples from the same test batch to minimize inter-batch variability, especially at high concentrations indicative of severe inflammation
- •This POC test cannot reliably replace the reference turbidimetric immunoassay for definitive SAA quantification; consider it a screening tool rather than a gold standard for clinical decision-making
- •Horses with heaves develop a hypercoagulable blood state that persists even during clinical remission, suggesting systemic involvement beyond the lungs
- •Management strategies should focus on reducing pulmonary inflammation to address both respiratory symptoms and underlying systemic coagulation abnormalities
- •Low-dust housing environments improve clinical signs but do not fully normalize blood coagulation parameters in heaves-affected horses
- •Screen horses at risk of laminitis for insulin dysregulation using oral sugar or glucose tolerance tests to enable early intervention
- •Manage hyperinsulinaemia through dietary modification and weight control, as insulin dysregulation significantly increases laminitis risk
- •Consider insulin dysregulation in foals presenting with prematurity or systemic illness, as it can accompany these conditions
Key Research Findings
Doramapimod was well tolerated with no adverse effects or clinicopathological changes in safety study
Doramapimod-treated horses showed significantly lower heart rates (P=0.03) and rectal temperatures (P=0.03) after LPS infusion compared to placebo
TNF-α and IL-1β concentrations were significantly lower in doramapimod-treated horses (P=0.03) following LPS challenge
White blood cell count was significantly higher in doramapimod-treated horses (P=0.03), suggesting decreased leukocyte activation
Meloxicam administered 60 minutes prior to LPS infusion significantly reduced pain scores at 90 minutes (P < 0.01) and 180 minutes (P < 0.05) compared to control
Meloxicam showed analgesic efficacy in a low-dose equine endotoxin model without significant effects on systemic inflammatory markers (TNF-α, cortisol, leukocyte counts)
COX-2 preferential inhibition by meloxicam demonstrated clinical benefit in acute inflammatory pain without the documented gastrointestinal side effects associated with non-selective NSAIDs like flunixin meglumine
22 inflammation-related genes in peripheral blood leukocytes were measured to differentiate local versus systemic inflammation responses in horses
Expression profiles using RT-qPCR and hierarchical clustering successfully distinguished between LPS-induced acute synovitis (local inflammation) and LPS-induced endotoxemia (systemic inflammation)
Gene expression patterns in peripheral blood leukocytes can characterize the transition from local to systemic inflammatory states in equine models
High non-structural carbohydrate (NSC) diet promoted increased serum TNF (inflammatory marker) compared to fat-based diet despite similar weight gain in both groups
Fat-based diet feeding for 12 weeks decreased circulating TNF concentrations, an effect largely maintained throughout the 32-week study
No linear correlation found between serum TNF concentration and body condition score as horses increased from BCS 4 to 7
Diet composition influenced systemic inflammation independent of weight gain, suggesting NSC may promote low-grade inflammation even during weight gain phase
Horses that did not survive colic showed markedly lower erythrocyte sedimentation rate (ESR) values at hospital admission compared to survivors
Evidence Base
Effect of the p38 MAPK inhibitor doramapimod on the systemic inflammatory response to intravenous lipopolysaccharide in horses.
Bauquier Jennifer, Tudor Elizabeth, Bailey Simon (2020) — Journal of veterinary internal medicine
Oral Administration of Meloxicam Suppresses Low-Dose Endotoxin Challenge-Induced Pain in Thoroughbred Horses.
Urayama Shuntaro, Tanaka Akane, Kusano Kanichi et al. (2019) — Journal of equine veterinary science
Characterization and differentiation of equine experimental local and early systemic inflammation by expression responses of inflammation-related genes in peripheral blood leukocytes.
Vinther Anne Mette L, Heegaard Peter M H, Skovgaard Kerstin et al. (2016) — BMC veterinary research
Effects of Diet and Weight Gain on Body Condition Scoring in Thoroughbred Geldings
Suagee Jessica K., Burk Amy O., Quinn Rachael W. et al. (2008) — Journal of Equine Veterinary Science
Prognostic Significance of Erythrocyte Sedimentation Rate for Survival in Equine Colic
F. Meistro, R. Rinnovati, E. Blanc et al. (2026) — Animals : an Open Access Journal from MDPI
Integration of machine learning and viscoelastic testing to improve survival prediction in horses experiencing acute abdominal pain at a veterinary teaching hospital.
Macleod, Wilkins, McCoy et al. (2025) — Equine veterinary journal
Arthrospira platensis enriched with Cr(III), Mg(II), and Mn(II) ions improves insulin sensitivity and reduces systemic inflammation in equine metabolic affected horses.
Artur Tomal, Jolanta Szłapka-Kosarzewska, Małgorzata Mironiuk et al. (2024) — Frontiers in endocrinology
The combination of trailer transport and exercise increases gastrointestinal permeability and markers of systemic inflammation in horses.
McGilloway Melissa, Manley Shannon, Aho Alyssa et al. (2023) — Equine veterinary journal
Investigation of two different human d-dimer assays in the horse.
Honoré Marie Louise, Pihl Tina H, Busk-Anderson Tanne M et al. (2022) — BMC veterinary research
Metabogenomics reveals four candidate regions involved in the pathophysiology of Equine Metabolic Syndrome.
L. Patterson Rosa, M. Mallicote, M. Long et al. (2020) — Molecular and cellular probes
Disparate effects of LPS infusion and carbohydrate overload on inflammatory gene expression in equine laminae.
Kwon, Moore, Robertson et al. (2014) — Veterinary immunology and immunopathology
Clinical features and treatment response to differentiate idiopathic peritonitis from non-strangulating intestinal infarction of the pelvic flexure associated with Strongylus vulgaris infection in the horse.
Hedberg-Alm Ylva, Tydén Eva, Tamminen Lena-Mari et al. (2022) — BMC veterinary research
Effects of intravenous administration of peripheral blood-derived mesenchymal stromal cells after infusion of lipopolysaccharide in horses.
Taylor Sandra D, Serpa Priscila B S, Santos Andrea P et al. (2022) — Journal of veterinary internal medicine
Spirulina platensis Improves Mitochondrial Function Impaired by Elevated Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells (ASCs) and Intestinal Epithelial Cells (IECs), and Enhances Insulin Sensitivity in Equine Metabolic Syndrome (EMS) Horses
D. Nawrocka, K. Kornicka, Agnieszka Śmieszek et al. (2017) — Marine Drugs
The use of liquid chromatography tandem mass spectrometry to detect proteins in saliva from horses with and without systemic inflammation.
Jacobsen Stine, Top Adler Ditte Marie, Bundgaard Louise et al. (2014) — Veterinary journal (London, England : 1997)
Red maple (Acer rubrum) leaf toxicosis in horses: a retrospective study of 32 cases.
Alward Ashley, Corriher Candice A, Barton Michelle H et al. (2006) — Journal of veterinary internal medicine
Neutrophil-Extracellular Traps, Cell-Free DNA, and Immunothrombosis in Companion Animals: A Review.
Goggs Robert, Jeffery Unity, LeVine Dana N et al. (2020) — Veterinary pathology
Comparative Anti-inflammatory Effects of Insulin and Flunixin on Acute-Phase Responses and Cardiovascular Biomarkers During Inflammatory Phase in Miniature Donkeys.
Samimi Amir Saeed, Samimi Kamyab, Karimiafshar Marzieh et al. (2019) — Journal of equine veterinary science
Analytical validation of a new point-of-care assay for serum amyloid A in horses.
Schwartz D, Pusterla N, Jacobsen S et al. (2018) — Equine veterinary journal
Blood hypercoagulability and systemic inflammation in horses with heaves.
Leclere Mathilde, Bédard Christian, Cortes-Dubly Marie-Laure et al. (2015) — Veterinary journal (London, England : 1997)