The effects of recombinant interleukin-1 and recombinant tumor necrosis factor on non-specific resistance to infection.
Natural and synthetic immunomodulators that increase non-specific resistance to infection induce the production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Therefore, we investigated the effect of IL-1 and of TNF on the survival of lethally-infected mice. Mice were injected with 1 x 10(6) Klebsiella pneumoniae in the thigh muscle. When recombinant human IL-1 beta was given as a single i.p. injection 24 h before the infection, survival was increased. Using 80 ng IL-1 beta per mouse, survival compared to control animals was 80% versus 20% 48 h after the infection (p less than 0.001). No effect of IL-1 was observed when it was given 1/2 h before or 6 h after the infection. IL-1 alpha proved to be at least as potent as IL-1 beta. Numbers of bacteria cultured from the blood, thigh muscle, liver, spleen, and kidney were similar in IL-1-treated and control animals. Protection against death by IL-1 was also investigated in granulocytopenic mice with a Pseudomonas aeruginosa infection. Administration of the cyclooxygenase-inhibitor, ibuprofen, did not affect the beneficial effect of IL-1. In this model human recombinant TNF was at least tenfold less active than IL-1 beta. Pretreatment with IL-1 also had a significant effect on survival of mice that received a high dose of bacterial lipopolysaccharide.
van der Meer
J W
JW
Department of Infectious Diseases, University Hospital Leiden, The Netherlands.
D000276:Adjuvants, Immunologic; D000818:Animals; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D007710:Klebsiella Infections / Q000276:immunology* / Q000382:microbiology; D007711:Klebsiella pneumoniae; D051379:Mice; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D004731:Endotoxins; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007052:Ibuprofen