INTRATRACHEAL ADMINISTRATION OF ENDOTOXIN AND CYTOKINES .7. THE SOLUBLE INTERLEUKIN-1 RECEPTOR AND THE SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR-II (P80) INHIBIT ACUTE-INFLAMMATION

Intratracheal administration of endotoxin (LPS) causes acute neutrophi lic inflammation via induction of pulmonary tumor necrosis factor alph a (TNF) and interleukin-1 (IL-1) expression. In the present study, the anti-inflammatory activity of soluble IL-1 receptor (sIL-1r) and solu ble TNF receptor p80 (sTNFr-p80) in LPS-induced acute pulmonary inflam mation was investigated. The sIL-1r coinjected intratracheally with LP S in rats significantly inhibits neutrophilic exudation into bronchoal veolar lavage (BAL) fluid by 47% after 6 hr compared to injection of L PS alone. TNF and IL-6 in the same BAL fluids were both lowered by app roximately 50% after intratracheal coinjection of sIL-1r and LPS as co mpared to LPS alone. In the same model, the sTNFr-p80 inhibited acute inflammation. Paradoxically, TNF levels in BAL fluids were generally e levated after the intratracheal coinjection of LPS and monomeric sTNFr -p80 compared to injection of LPS injection alone. The combined anti-i nflammatory effect of sIL-1r and sTNFr-p80 at the maximally effective individual doses is not significantly greater than the effect of eithe r soluble receptor alone. (C) 1994 Academic Press, Inc.