A low dose of recombinant interleukin 1 protects granulocytopenic mice from lethal gram-negative infection.
Natural and synthetic immunomodulators that increase nonspecific resistance to infection induce interleukin 1 (IL-1) production. Therefore, we investigated the effect of the administration of IL-1 on the survival of lethally infected granulocytopenic mice. Mice with cyclophosphamide-induced granulocytopenia were injected with approximately 10(7) Pseudomonas aeruginosa in the thigh muscle at time 0; gentamicin was administered 6 hr and 23 hr later. When recombinant human IL-1 beta (one of the two forms of IL-1) was given as a single i.p. injection 24 hr before the infection, survival was increased. Using 80 ng of IL-1 beta per mouse, survival compared to control animals was 98% vs. 71% at 24 hr, 98% vs. 60% at 30 hr, 86% vs. 36% at 36 hr, and 61% vs. 11% at 48 hr (P less than 0.001) after the infection. No effect of IL-1 was observed when it was given 0.5 hr before or 6 hr after the infection. Animals not treated with gentamicin also benefited from the IL-1. Administration of the cyclooxygenase inhibitor ibuprofen did not affect the activity of IL-1. Numbers of bacteria cultured from the blood, thigh muscle, liver, spleen, and kidney were similar in IL-1-treated and control animals. Superoxide production by peritoneal macrophages was also similar in the two groups. These studies demonstrate that IL-1 pretreatment protects granulocytopenic mice against lethal pseudomonas infection and suggest that this protection occurs through a noncellular mechanism.
D000380:Agranulocytosis / Q000276:immunology*; D000818:Animals; D001770:Blood Bactericidal Activity; D004306:Dose-Response Relationship, Immunologic; D007167:Immunotherapy; D007375:Interleukin-1 / Q000627:therapeutic use*; D051379:Mice; D011552:Pseudomonas Infections / Q000628:therapy*; D011550:Pseudomonas aeruginosa; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013290:Streptococcal Infections / Q000628:therapy*; D013296:Streptococcus pneumoniae
D007375:Interleukin-1; D011994:Recombinant Proteins