24th Annual Meeting of the British Society of Toxicological Pathologists: Biomarkers of Safety and Pharmacology. Meeting Abstracts

Abstract

Systemic inflammatory response syndrome (SIRS) is a ‘‘state of whole body inflammation’’ that can result in multiple organ dysfunction (MOD) circulatory collapse and even death. SIRS is considered as a self-defense mechanism to nonspecific insults that arise from chemical, necrotic (as a result of tissue damage), ischemic, or infectious stimuli that induce organ pathology. SIRS and MOD are complex processes that involve hemodynamic, humoral and cellular responses, complement activation, and cytokine cascade. SIRS and MOD develop in stages that are mediated in part through acute phase proteins, cytokine dysregulation, and hemodynamic events. In toxicology studies, safety evaluation of xenobiotics, pharmacologically active immune stimulants, and immunosuppressants can induce SIRS and MOD in rats, dogs, and nonhuman primates, and therefore, measurement of circulating mediators as biomarkers of SIRS and MOD will enable clinicians to avoid a potentially severe catastrophic event. Furthermore, chemically induced pathology resulting from events such as ischemia, extensive tissue damage and necrosis, and activation and release of stress hormones all can induce SIRS and MOD as a secondary toxic response. Whole-body SIRS is considered an adverse finding in preclinical toxicology studies. Therefore, knowledge and use of the appropriate inflammatory biomarkers that reflect this pathological process is quite useful both preclinically and clinically. Additionally, preclinical and clinical monitoring of biomarkers that are early predictors or reporters of SIRS are valuable to the toxicologist in hazard identification and risk assessment of novel therapeutics with the potential to cause a proinflammatory response.