Interleukin-1beta 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 produced. Alterations in CD4 and CD8 lymphocytes after experimental endotoxic challenge and their correlation with the protective effects of interleukin-1beta (IL-1beta) and ibuprofen pretreatment were investigated. CBA/H mice were injected with lipopolysaccharide (LPS) of Escherichia coli (125 mg/kg); 40 mice were pretreated with IL-1beta (80 ng/mouse, 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). Prostaglandin E2 (PGE2) urine levels were determined 4, 8, and 12 hr post-LPS (10 mice), CD4 and CD8 cells 24 hr post-LPS (10 mice), and mortality at 24, 48, 72, and 96 hr (20 mice). PGE2 decreased in ibuprofen-treated groups (P < 0.05 versus control, IL-1beta groups). CD4/CD8 ratio increased in groups treated with IL-1beta (11,9) and IL-1beta plus ibuprofen (11,2) compared with sham (3,4), LPS (4,2), and ibuprofen alone (4,1) (P < 0.05). Mortality decreased in all treated groups. A correlation was observed between IL-1beta treatment, CD4/CD8 ratio, and reduced mortality. In this model IL-1beta treatment improved survival after endotoxin challenge, preventing lymphocyte derangements and increasing CD4/CD8 ratio. This effect was not potentiated by ibuprofen administration.