IL-6 vermittelt protektive Effekte des DHEA bei einer polymikrobiellen Sepsis

Abstract

Sepsis is a frequent complication in the posttraumatic course on the intensive care unit. Cytokines play an important role. High levels of IL-6 correspond to bad prognosis. Complications in septic patients derive from immunologic dissonance. This disturbance may be modulated by the steroid hormone dehydroepiandrosterone (DHEA). The purpose of this study was to investigate if DHEA affects mortality in a cecal ligation and puncture-induced sepsis model through IL-6 by means of knocking out this gene. The mortality of mice undergoing CLP (WT: 46%, IL-6^−/−: 58%) could be reduced by DHEA for WT mice only (WT: 12%, IL-6^−/−: 60%). A diminished cytokine secretion in the wildtype mice treated with DHEA accompanied this reduction. In the knock out mice no TNF-α or IL-6 secretion could be measured. However, IL-10 levels were extremely high in CLP mice without DHEA treatment. IL-6 substitution restored the state as in WT mice. This implies that DHEA exerts part of its effects via IL-6. Nevertheless, a cytokine independent pathway may be assumed for the protective effects of DHEA.