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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0303108

Received for publication March 17, 2003.
Revised June 30, 2003.
Accepted for publication July 1, 2003.

Article

Sepsis-induced SOCS-3 expression is immunologically restricted to phagocytes

P. S. Grutkoski , Y. Chen , C. S. Chung , and A. Ayala @

Division of Surgical Research, Rhode Island Hospital and Brown University Medical School, Providence

@ To whom correspondence should be addressed. E-mail: aayala{at}lifespan.org.


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Abstract

We have shown that immune cells from septic mice exhibit a suppressed response to exogenous stimuli in vitro. The suppressors of the cytokine signaling (SOCS) family are proteins that block intracellular signaling and can be induced by inflammatory mediators. Therefore, we hypothesized that SOCS-3 is up-regulated in immune cells in response to a septic challenge induced by cecal ligation and puncture (CLP). Mice were subjected to CLP or sham-CLP, and 2-48 h later, the blood, thymus, spleen, lung, and peritoneal leukocytes were harvested and examined. SOCS-3 was undetectable in thymocytes or blood leukocytes. In contrast, SOCS-3 was up-regulated in the spleen, lung, and peritoneal leukocytes in a time-dependent manner. Further examination revealed that only the macrophages and neutrophils expressed SOCS-3. These data suggest that cytokines and bacterial toxins present during sepsis have the ability to suppress the cytokine and/or lipopolysaccharide response and the function of immune cells by up-regulating SOCS-3.

Key Words: macrophage • neutrophil • immunosuppression • CLP • mouse




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