Splenic immune suppression in sepsis: A role for IL-10-induced changes in p38 MAPK signaling

Grace Y. Song, Chun Shiang Chung, Martin G. Schwacha, Doraid Jarrar, Irshad H. Chaudry, Alfred Ayala

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Background. Studies have indicated that following the induction of sepsis, there is a late (24 h) generalized suppression of the immune response which is associated with increased anti-inflammatory mediator release (e.g., IL-10). However, the mechanisms by which this occurs are unknown. In this regard, recent studies indicate that p38 mitogen-activated protein kinase (p38 MAPK) may play a central role in transducing the signals from immunosuppressive agents which in turn may alter lymphoid cytokine release. The aim of this study, therefore, was to determine whether the anti- inflammatory mediator IL-10 alters splenocyte IL-2 and IFN-γ release, as well as the expression and activation of p38 MAPK in septic animals. Materials and methods. Splenocytes (SPL) (or for some experiments purified T cells) were harvested from mice subjected 24 h earlier to either sepsis by cecal ligation and puncture (CLP) or Sham-CLP and stimulated with 2.5 μg concanavalin A (ConA)/ml in the presence or absence of either monoclonal antibody (Mab) to IL-10 (4 μg/ml) or IgG control. In subsequent studies, sepsis was induced in C57BL/6J and C57BL/6 IL-10 knockout mice, and SPL harvested and stimulated with ConA. SPL cytokine release was measured by ELISA, and the expression and phosphorylation of p38 MAPK were measured by Western analysis. Results. The results indicate that Th1 cytokine (IL-2, IFN- γ) release was depressed by sepsis, while p38 MAPK expression and activity were increased in SPL as well as in T-cells. Neutralization of IL-10 by in vitro use of anti-IL-10 Mab and in the IL-10 knockout animal restored the Th1 response and caused a downregulation of p38 MAPK expression and activity after CLP. Thus, IL-10 appears to contribute to the increase in p38 MAPK activity and expression and the corresponding suppression of Th1 response seen in late sepsis.

Original languageEnglish (US)
Pages (from-to)36-43
Number of pages8
JournalJournal of Surgical Research
Volume83
Issue number1
DOIs
StatePublished - May 1 1999
Externally publishedYes

Keywords

  • Cecal ligation and puncture
  • IL-10
  • Mouse
  • P38 MAPK
  • Splenocytes
  • T-lymphocytes

ASJC Scopus subject areas

  • Surgery

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