Intratracheal administration of endotoxin and cytokines. VII. The soluble interleukin-1 receptor and the soluble tumor necrosis factor receptor II (p80) inhibit acute inflammation

Clin Immunol Immunopathol. 1994 Jul;72(1):137-40. doi: 10.1006/clin.1994.1117.


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.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Endotoxins / administration & dosage
  • Endotoxins / antagonists & inhibitors*
  • Inflammation / immunology
  • Inflammation / prevention & control*
  • Interleukin-6 / biosynthesis
  • Intubation, Intratracheal
  • Lipopolysaccharides / antagonists & inhibitors
  • Male
  • Rats
  • Rats, Inbred Lew
  • Receptors, Interleukin-1*
  • Receptors, Tumor Necrosis Factor*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Solubility
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Endotoxins
  • Interleukin-6
  • Lipopolysaccharides
  • Receptors, Interleukin-1
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha