Prostaglandin E-2 down-regulation of T cell IL-2 production is independentof IL-10 during gram-negative sepsis

The present study ascertained the role of PGE, in sepsis associated modulat ion 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 Escheri chia coli (100-150 CFU) and Bacteroides fragilis (10(4) CFU) into the abdom inal cavity. Animals implanted with fecal pellets without the bacteria were designated as sterile. For the assessment of PGE, role in sepsis, a group of septic and sterile rats were pretreated with indomethacin to inhibit end ogenous PGE, synthesis. Splenic T cells were obtained 48 h after septic or sterile implantations, and their IL-2 and IL-IO production was measured. A significant suppression in the levels of IL-2 production and mRNA expressio n was observed in T cells from septic rats compared with the T cells from s terile and control rats. IL-IO protein and mRNA expression was found to be significantly higher in septic rat T cell compared to sterile and control r at 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 PGE, released during sepsis can cause T c ell 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. (C) 1 999 Elsevier Science B.V. All rights reserved.