Journal
SHOCK
Volume 22, Issue 5, Pages 423-430Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.shk.0000142184.49976.0c
Keywords
septic shock; reprogramming; classically and alternatively activated macrophages
Funding
- NIAID NIH HHS [AI44908, R37AI23447] Funding Source: Medline
- NIGMS NIH HHS [GMHL 37704-13] Funding Source: Medline
- CSRD VA [IK2 CX000643] Funding Source: Medline
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To monitor and better understand the immunoinflammatory sequelae in sepsis and septic shock, systemic and monocyte-related cytokine responses were evaluated in baboons with experimental peritonitis induced by an E coli-laden fibrin clot. Despite similar bacterial inocula, considerable interindividual variability in clinical manifestation and outcome of infection was observed. Because monocytes and macrophages are a key component of innate immunity, we hypothesized that early polarization of distinct activation programs in circulating monocytes that culminates in the emergence of either classically (M1) or alternatively (M2) activated monocytes may underlie the observed susceptibility or resistance to infection. To test our hypothesis, we analyzed infection-induced expression of cytokine mRNAs in monocytes isolated from surviving and dead animals. Our data show that resistance to E. coli sepsis may well be associated with a mixed M1/M2 activation state of circulating monocytes, whereas M1 phenotype appeared to be prevailing in monocytes from animals that died. Together with data on systemic cytokine responses, the latter findings indicate that morbidity and mortality of animals with gram-negative sepsis may well result from an overwhelming proinflammatory response. Collectively, our data contribute to a better understanding of cytokine networking in the immunoinflammatory response to microbial infection and suggest M1/M2 immunophenotypic profiling of readily available circulatory monocytes for early prognosis of severe infections.
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