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Endogenous IL‐10 Regulates Sepsis‐induced Thymic Apoptosis and Improves Survival in Septic IL‐10 Null Mice
Author(s) -
Tschoeke S. K.,
Oberholzer C.,
LaFace D.,
Hutchins B.,
Moldawer L. L.,
Oberholzer A.
Publication year - 2008
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2008.02176.x
Subject(s) - apoptosis , sepsis , endogeny , immunology , proinflammatory cytokine , programmed cell death , ligation , biology , lymphocyte , caspase 1 , cytokine , inflammation , interleukin 10 , medicine , endocrinology , biochemistry
Recent studies have shown that increased lymphocyte apoptosis contributes to sepsis‐induced mortality. Furthermore, studies have demonstrated that IL‐10 can suppress lymphocyte apoptosis, in part, by upregulating Bcl‐2 expression and interfering with activation induced cell death. We have previously shown that intrathymic delivery of IL‐10 with an adenoviral vector in wild‐type mice significantly improves outcome to sepsis. Presently, we investigated the role of endogenous IL‐10 expression on thymocyte apoptosis and outcome in IL‐10 null mice subject to induction of generalized polymicrobial peritonitis via cecal ligation and puncture. Compared to wild‐type C57BL/6 mice, IL‐10 null mice demonstrated increased mortality and enhanced lymphocyte apoptosis. Intrathymic injection with an adenoviral vector expressing human IL‐10 prior to cecal ligation and puncture in IL‐10 null mice significantly improved outcome and decreased thymic caspase‐3 activity. Furthermore, plasma concentrations of IL‐6 were also significantly reduced in IL‐10 null mice treated with the IL‐10 expressing adenovirus. In contrast, injection of a control adenovirus did not improve outcome in IL‐10 null mice, nor was caspase‐3 activity reduced. Thus, local thymic expression of IL‐10 not only improves outcome but also reduces local tissue apoptosis and caspase‐3 activity, and appears to attenuate the systemic proinflammatory cytokine response.