Age- and gender-related differences of the immune function in a murine model of hemorrhagic shock: IL-10 restores immunodepression in aged females without reduction of mortality |
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Authors: | Soeren Torge Mees Christoph Dohm Kerstin Broetzmann Joerg Schroeder Fred Faendrich Bernd Kremer Volker Kahlke |
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Institution: | (1) Department of General Surgery, University of Muenster, Waldeyerstr. 1, 48147 Muenster, Germany;(2) Department of General Surgery, University of Kiel, 24105 Kiel, Germany |
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Abstract: | Introduction Interleukin-10 (IL-10) treatment has been shown to have beneficial effects on the immune function after hemorrhagic shock
and to improve survival after subsequent sepsis in young male mice, but not in young females. Although it was demonstrated
that the immune function under these conditions is reversed with age, it remains unclear whether the observed gender-related
effect of IL-10 treatment continues to exist in aged mice.
Materials and methods Aged male and female CBA/J mice (18–19 months) were subjected to hemorrhage (35 ± 5 mmHg for 90 min) or sham operation. At
resuscitation, each received either 10-μg recombinant murine (rm)IL-10 or placebo i.p. At 48 h after resuscitation, either
the mice were killed and the plasma, splenic macrophages (sMϕ), and splenocytes were harvested or polymicrobial sepsis was
induced by cecal ligation and puncture (CLP). After CLP, either survival over 10 days was determined or, 4 h after CLP, tissues
were again harvested and cytokine-released in vitro were assessed by enzyme-linked immunosorbent assay.
Results Early IL-10 treatment restored depressed proinflammatory immune response (TNF-α, IL-1β) and Th1 response of splenocytes in
aged females after hemorrhage, whereas having no effects or having suppressive effects in aged males. Subsequent sepsis combined
with placebo treatment led to a significant suppression of proinflammatory cytokine release of sMϕ and a significant increase
of Th2 response in both males and females associated with high mortality (80–100%, respectively) after CLP. These effects
were not influenced by early rmIL-10 treatment.
Conclusion After hemorrhage, early rmIL-10 treatment restored immune function in aged females, but not in males. However, in contrast
to young mice, rmIL-10 treatment had no effect on survival and immune function after CLP in aged mice.
The paper was presented at the first joint meeting of the Surgical Infection Society (SIS–NA) and the Surgical Infection Society–Europe
(SIS–E), 02.-04.05.2002, Madrid, Spain, and published as an abstract in Surgical Infections 3(1):70, 2002. |
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Keywords: | Gender Tumor necrosis factor-α Interleukin Hormones Double-hit |
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