This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Hukkanen, R. R. Articles by Frevert, C. W. PubMed PubMed Citation Articles by Hukkanen, R. R. Articles by Frevert, C. W. Social Bookmarking                         What's this?

Systemic Inflammatory Response Syndrome in Nonhuman Primates Culminating in Multiple Organ Failure, Acute Lung Injury, and Disseminated Intravascular Coagulation

¹ University of Washington, Department of Comparative Medicine, Seattle, Washington 98195-7190, USA
² Washington National Primate Research Center, Seattle, Washington 98195-7330, USA
³ University of Washington, Department of Medicine, Division of Pulmonary and Critical Care, Seattle, Washington 98195, USA

Correspondence: Renee Rosemary Hukkanen, Washington National Primate Research Center, University of Washington, Health Science Complex I-421 Box 357330, Seattle, Washington 98195-7330, USA; e-mail:rgamboa{at}wanprc.org.

The systemic inflammatory response syndrome (SIRS) is a clinicopathological manifestation of overexuberant acute-phase inflammation caused by infectious or noninfectious etiologies. The systemic release of pro-inflammatory cytokines, chemokines, and lipid and vasoactive mediators induces endothelial damage and microvascular thrombosis, potentially culminating in disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), and multiple organ dysfunction (MOD) or failure (MOF). We present five cases in the pig-tailed macaque and olive baboon where SIRS resulted in MOF, ARDS, DIC, and the Waterhouse-Friderichsen syndrome; each with gross and histological elements manifested as edema, deposition of fibrin, hemorrhage, and thrombosis. In the described cases, SIRS was the end-common pathway for multiple risk factors that parallel those documented in humans: major surgery, obstetric complications, and infection. The diagnosis of SIRS should be considered when evaluating nonhuman primate (NHP) cases of MOF manifesting with histological evidence of vascular leakage. Experimental manipulation of NHP models may be complicated by SIRS and accompanying rapid clinical decompensation. Such adverse events may compromise toxicological studies and should be avoided when possible.

Key Words: acute respiratory distress syndrome (ARDS) • disseminated intravascular coagulation (DIC) • immunopathology • inflammation • multiple organ failure/multiple organ dysfunction (MOF/MOD) • primate pathology • systemic inflammatory response syndrome (SIRS)

Abbreviations: Alk, alkaline phosphatase • ARDS, acute respiratory distress syndrome • BCNU, 06-benzylguanine • BUN, blood urea nitrogen • Crt, creatinine • DIC, disseminated intravascular coagulation • GGT, -glutamyl transferase • GVHD, graft-verus-host disease • Hb, hemoglobin • HCT, hematocrit • IL-1β, interleukin 1 β • IL-6, interleukin 6 • IL-8, interleukin 8 • MOF, multiple organ failure • NHP, nonhuman primate • SGOT, serum glutamic oxaloacetic transaminase • SGPT, serum glutamic pyruvic transaminase • SIRS, systemic inflammatory response syndrome • TLR, Toll-like receptor • TNF-, tumor necrosis factor- • WBC, white blood cell • WHF, Waterhouse-Friderichsen syndrome

Toxicologic Pathology, Vol. 37, No. 6, 799-804 (2009)
DOI: 10.1177/0192623309343778


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?