Intratracheal administration of endotoxin and cytokines. VII. The soluble interleukin-1 receptor and the soluble tumor necrosis factor receptor II (p80) inhibit acute inflammation.
Intratracheal administration of endotoxin (LPS) causes acute neutrophilic inflammation via induction of pulmonary tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) expression. In the present study, the anti-inflammatory activity of soluble IL-1 receptor (sIL-1r) and soluble TNF receptor p80 (sTNFr-p80) in LPS-induced acute pulmonary inflammation was investigated. The sIL-1r coinjected intratracheally with LPS in rats significantly inhibits neutrophilic exudation into bronchoalveolar lavage (BAL) fluid by 47% after 6 hr compared to injection of LPS alone. TNF and IL-6 in the same BAL fluids were both lowered by approximately 50% after intratracheal coinjection of sIL-1r and LPS as compared to LPS alone. In the same model, the sTNFr-p80 inhibited acute inflammation. Paradoxically, TNF levels in BAL fluids were generally elevated after the intratracheal coinjection of LPS and monomeric sTNFr-p80 compared to injection of LPS injection alone. The combined anti-inflammatory effect of sIL-1r and sTNFr-p80 at the maximally effective individual doses is not significantly greater than the effect of either soluble receptor alone.
Department of Pathology, San Diego School of Medicine, University of California.
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D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004731:Endotoxins / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D015850:Interleukin-6 / Q000096:biosynthesis; D007442:Intubation, Intratracheal; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha