ISSN 2398-2977      

Systemic inflammatory response syndrome


Synonym(s): SIRS, endotoxemia


  • A syndrome not a discrete disease with many initiating factors, both infectious and non-infectious.
  • A globalized, dysregulated systemic inflammatory of high intensity response to a variety of clinical insults which can lead to organ dysfunction and failure.
  • Often linked to infection and becomes sepsis.
  • Non-infectious causes include perinatal asphyxia syndrome   Perinatal asphyxia  , strangulating gastrointestinal lesions, eg strangulating lipoma, large colon volvulus.
  • May be associated with endotoxemia; endotoxemia is a specific form of SIRS caused by the presence of endotoxin (lipopolysaccharide, LPS).
  • Signs: hyperthermia or pyrexia, tachycardia, tachypnea.
  • Diagnosis: clinical signs, leukopenia or leukocytosis with a left shift (increased band cells).
  • Treatment: treat underlying condition.
  • Prognosis: guarded.



  • Inflammatory cascade is activated by infectious or non-infectious stimuli.
  • Initially protective, but becomes destructive.
  • Over production of pro-inflammatory mediators and under production of anti-inflammatory mediators.
  • A progressive process which can    →   multiple organ dysfunction progressing to organ failure.


  • Relate to the underlying cause, eg failure of passive transfer in neonates increases risk of SIRS and sepsis.


  • The mediators include:
    • Cytokines, eg tumor necrosis factor alpha (TNF-alpha) and interleukins (IL), particularly IL1 and IL6.
    • Platelet activating factor.
    • Lipid-derived mediators including prostaglandins, thromboxanes and leukotrienes.
    • Coagulation factors.
    • Reactive oxygen species.
  • Cytokines:
    • Soluble glycoproteins involved in specific immune responses and act as inflammatory mediators.
    • Circulating concentrations of certain cytokines, eg TNF-alpha and interleukins, have been shown to be linked with morbidity and mortality in SIRS cases.
    • Sepsis cases, ie those associated with infection will have more TNF-alpha released therefore more IL-6 and IL-8 released and this is associated with a higher fever.
  • Tissue injury occurs during inflammation:
    • The acute (initial) phase of inflammation caused by tissue injury or inflammation   →   complement activation and causes tissue macrophages, monocytes, mast cells, endothelial cells and platelets to release mediators, eg TNF-alpha and IL-1. These mediators have local and systemic effects which initiate several cascades. They are responsible for causing severe lung injury, hypotension, fever and release of stress hormones (norepinephrine, vasopressin, activation of the renin-angtiotensin-aldosterone system).
    • Stromal cells release the second wave of mediators, eg IL-6, causing fever and the release of pituitary hormones and the liver to synthesize acute phase proteins, eg C-reactive protein, fibrinogen and major anti-proteases. In addition, IL-8 and interferon gamma are produced.
    • The pro-inflammatory interleukins either function directly on tissue or work via secondary mediators to activate the coagulation cascade and the complement cascade and the release of nitric oxide, platelet-activating factor, prostaglandins and leukotrines.
    • IL-1 and TNF-alpha directly affect endothelial surfaces, leading to the expression of tissue factor. Tissue factor initiates the production of thrombin, thereby promoting coagulation, and is a pro-inflammatory mediator itself. Fibinolysis is impaired by IL-1 and TNF-alpha via production of plasminogen activator inhibitor-1. Pro-inflammatory cytokines also disrupt the naturally occurring anti-inflammatory mediators antithrombin and activated protein-C (ACP). If unchecked, this coagulation cascade leads to complications of icrovascular thrombosis, including organ dysfunction.
    • At the site of the insult the mediators cause pain, vasodilation, increased vascular permeability and attract granulocytes.
    • This acute phase occurs within 1-4 h of the initial insult.
    • Associated with the interaction of neutrophils with the vascular endothelium.
    • A three stage process of rolling, adhesion and migration occurs allowing the neutrophils to migrate into the tissues.
    • Tissue injury occurs due to the degranulation of proteases and the production of reactive oxygen species.
  • Under normal conditions the pathophysiological features of inflammation have subsided by 24-48 h. IL-4 and IL-10 act as anti-inflammatory mediators and reduce TNF-alpha and IL-1, IL-6 and IL-8 production, antagonists to the TNF-alpha and IL-1 receptors are produced and cortisone reduces the response. In SIRS this anti-inflammatory action is reduced or is overwhelmed.


  • Dependent upon the severity of the primary lesion and prompt aggressive treatment.


  • In a study of critically ill foals presented to a teaching hospital clinic for evaluation and treatment, the presence of SIRS was based on meeting at least 2 of the following criteria:
    • Leukocytosis, leukopenia or >10% immature band neutrophils, hyperthermia or hypothermia, tachycardia, tachypnea and evidence of sepsis. >40% of the foals evaluated had a diagnosis of SIRS.
    • Using a slightly modified set of criteria (leukocytosis, leukopenia or >10% immature band neutrophils, hyperthermia, tachycardia and tachypnea), nearly 30% of adult horses presented for evaluation and treatment of colic had evidence of SIRS.


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Further Reading


Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Moore J N & Vandenplas M L (2014) Is it the systemic inflammatory response syndrome or endotoxemia in horses with colic? Vet Clin North Am Equine Pract 30 (2), 337-351 VetMedResource.
  • Lewis D H et al (2012) The immunopathology of sepsis: Pathogen recognition, systemic inflammation, the compensatory anti-inflammatory response, and regulatory T-cells. J Vet Intern Med 26 (3), 457-482 PubMed.
  • Hashimoto-Hill S et al (2011) Serial measurement of lactate concentration in horses with acute colitis. J Vet Intern Med 25 (6), 1414-1419 PubMed.
  • Hollis A R et al (2007) Blood glucose in horses with acute abdominal disease. J Vet Intern Med 21 (5), 1099-1103 PubMed.
  • Corley K T T, Donaldson L L & Furr M O (2005) Arterial lactate concentration, hospital survival, sepsis and SIRS in critically ill neonatal foals. Equine Vet J 37 (1), 53-59 PubMed.
  • Dallap B L (2004) Coagulopathy in the equine critical care patient. Vet Clin North Am Eq Pract 20 (1), 231-251 VetMedResource.
  • Paterson R L & Webster N R (2000) Sepsis and the systemic inflammatory response syndrome. J Royal College Surgeons 45, 178-182 PubMed.
  • Nystrom P (1998) The systemic inflammatory response syndrome: definitions and aetiology. J Antimicrobial Chemo Suppl A (4), 11-17 PubMed.
  • Rangel-Frausto M S et al (1995) The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA 11 (273(2)), 117-123 PubMed.

Other sources of information

  • Okana S et al (2003) Systemic Inflammatory Response Syndrome Criteria as an Index for Prognosis in Dogs. Proc 8th WCVA. Knoxville, Tennesse. September Scientific Poster 31.
  • Reinhart K & Meisner M (2002) Update in the Diagnosis of Sepsis. European Society of Anaesthesiologists Refresher Course. April.

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