Interleukin-1 (IL-1)-induced resistance to bacterial infection: role of the type I IL-1 receptor.
Pretreatment with a low dose of recombinant human interleukin-1 beta (IL-1) (3 to 30 micrograms/kg) 24 h before a lethal Pseudomonas aeruginosa infection prolongs survival in neutropenic mice. We investigated the role of the type I IL-1 receptor (IL-1RI) and IL-1RII in this IL-1-induced protection by using a specific IL-1 receptor antagonist (IL-1-Ra), which blocks effects mainly via IL-1RI. Pretreatment with IL-1Ra before IL-1 partially blocked the IL-1-induced enhanced survival, whereas pretreatment with a specific neutralizing monoclonal antibody to IL-1RI (35F5) eliminated the IL-1 induced protection. The nonapeptide fragment 163-171 of recombinant human IL-1 beta, which possesses the immunoadjuvant but not the inflammatory effect of the entire molecule via a non-receptor-mediated signal transduction process, did not reproduce the IL-1-induced protection. IL-1-induced protection was associated with reduced serum aspartate aminotransferase and alanine aminotransferase concentrations in conjunction with ameliorated histopathology of the liver. These findings may be due to reduced cytokine production and cytokine sensitivity of target cells after infection. We conclude that the IL-1-induced nonspecific resistance to infection is mediated by cells bearing IL-1RI and is associated with a reduction of liver damage.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001219:Aspartate Aminotransferases / Q000097:blood; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051379:Mice; D011552:Pseudomonas Infections / Q000276:immunology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D017472:Receptors, Interleukin-1 / Q000187:drug effects*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase