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.
BACKGROUND
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.


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-microg recombinant murine (rm)IL-10 or placebo i.p. At 48 h after resuscitation, either the mice were killed and the plasma, splenic macrophages (sM phi), 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-alpha, IL-1 beta) 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 sM phi 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.


CONCLUSIONS
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.
Mees
Soeren Torge
ST
Department of General Surgery, University of Muenster, Waldeyerstr. 1, 48147, Muenster, Germany. soerentorge.mees@ukmuenster.de
Dohm
Christoph
C
Broetzmann
Kerstin
K
Schroeder
Joerg
J
Faendrich
Fred
F
Kremer
Bernd
B
Kahlke
Volker
V
D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D004958:Estradiol / Q000097:blood; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects; D016753:Interleukin-10 / Q000097:blood / Q000494:pharmacology*; D018664:Interleukin-12 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011994:Recombinant Proteins / Q000494:pharmacology; D018805:Sepsis / Q000276:immunology; D012737:Sex Factors; D012771:Shock, Hemorrhagic / Q000276:immunology*; D013739:Testosterone / Q000097:blood; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D013739:Testosterone; D004958:Estradiol