Prostaglandin E2 down-regulation of T cell IL-2 production is independent of IL-10 during gram-negative sepsis.
The present study ascertained the role of PGE2 in sepsis associated modulation of IL-2 and IL-10 production by T cells. Sepsis was induced in 225-250 g male rats (Sprague Dawley) by implanting fecal pellets containing Escherichia coli (100-150 CFU) and Bacteroides fragilis (10(4) CFU) into the abdominal cavity. Animals implanted with fecal pellets without the bacteria were designated as sterile. For the assessment of PGE2 role in sepsis, a group of septic and sterile rats were pretreated with indomethacin to inhibit endogenous PGE2 synthesis. Splenic T cells were obtained 48 h after septic or sterile implantations, and their IL-2 and IL-10 production was measured. A significant suppression in the levels of IL-2 production and mRNA expression was observed in T cells from septic rats compared with the T cells from sterile and control rats. IL-10 protein and mRNA expression was found to be significantly higher in septic rat T cell compared to sterile and control rat T cells. Although, treatment of animals with indomethacin significantly prevented the sepsis-related suppression of IL-2 production, such treatment of animals was associated with a further upregulation of IL-10 production. These data suggest that although PGE2 released during sepsis can cause T cell IL-2 down-regulation, it may not mediate the T cell IL-10 upregulation. The IL-2 down-regulation may not be an effect of IL-10 upregulation.
Choudhry
M A
MA
Department of Physiology, and Burn & Shock Trauma Institute, Loyola University Chicago Medical School, Maywood, IL 60153, USA.
Ahmad
S
S
Ahmed
Z
Z
Sayeed
M M
MM
D000818:Animals; D001442:Bacteroides Infections / Q000276:immunology*; D001441:Bacteroides fragilis / Q000276:immunology*; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004926:Escherichia coli / Q000276:immunology*; D007213:Indomethacin / Q000627:therapeutic use; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D007376:Interleukin-2; D016753:Interleukin-10; D015232:Dinoprostone; D007213:Indomethacin