INTERLEUKIN-1-BETA AND IBUPROFEN EFFECTS ON CD4 CD8 CELLS AFTER ENDOTOXIC CHALLENGE/

Multiple organ failure is considered a consequence of autodestructive inflammatory response during which a state of immunosuppression is pro duced. Alterations in CD4 and CDS lymphocytes after experimental endot oxic challenge and their correlation with the protective effects of in terleukin-1 beta (IL-1 beta) and ibuprofen pretreatment were investiga ted. CBA/H mice were injected with lipopolysaccharide (LPS) of Escheri chia coli (125 mg/kg); 40 mice were pretreated with IL-1 beta (80 ng/m ouse, 24 hr pre-LPS), 40 with ibuprofen (1 mg/kg 1 hr pre-LPS, 1 mg/kg 30 min post-LPS), and 40 with both drugs (same doses and timing). Pro staglandin E(2) (PGE(2)) urine levels were determined 4, 8, and 12 hr post-LPS (10 mice), CD4 and CD8 cells 24 hr post-LPS (10 mice), and mo rtality at 24, 48, 72, and 96 hr (20 mice). PGE(2) decreased in ibupro fen-treated groups (P < 0.05 versus control, IL-1 beta groups). CD4/ C D8 ratio increased in groups treated with IL-1 beta (11,9) and IL-1 be ta plus ibuprofen (11,2) compared with sham (3,4), LPS (4,2), and ibup rofen alone (4,1) (P < 0.05). Mortality decreased in all treated group s. A correlation was observed between IL-1 beta treatment, CD4/CD8 rat io, and reduced mortality. In this model IL-1 beta treatment improved survival after endotoxin challenge, preventing lymphocyte derangements and increasing CD4/CD8 ratio. This effect was not potentiated by ibup rofen administration. (C) 1996 Academic Press, Inc.