Human recombinant interleukin-1 receptor antagonist (hrIL-1RA) inhibits prostaglandin E2 (PGE2) generation but not alkaline phosphatase activity in in vivo chronic granulomatous tissue induced by KMnO4

Immunol Lett. 1993 Jul;37(1):1-6. doi: 10.1016/0165-2478(93)90124-k.

Abstract

Interleukin-1, a soluble polypeptide, plays an important role in inflammatory reactions by increasing prostaglandin E2 (PGE2) generation. Human recombinant IL-1 receptor antagonist (hrIL-1ra) is a natural inhibitor of IL-1 which blocks its activity in several inflammatory states. In these studies we found that hrIL-1ra (250 mg/ml) inhibits the generation of PGE2, as measured by RIA method, in minced mouse granuloma tissue (700 mg) treated overnight with LPS (10-1000 ng/ml) or hrIL-1 beta (0.1-10 ng/ml). In addition, we show that hrIL-1ra (250 ng/ml) strongly inhibited IL-1 alpha and IL-1 beta, as measured by ELISA method, in the minced granuloma tissue treated overnight with LPS 1 micrograms/ml or IL-1 beta (10 ng/ml). The granuloma tissue induced in mice by a dorsal subcutaneous injection (0.2 ml) of a saturated solution (1:40 dilution) of KMnO4 crystals, presented an alkaline phosphatase activity which was not inhibited by two intraperitoneal administrations of hrIL-1ra 20 micrograms/200 ml bolus injections (given at the same time as KMnO4 injection and one 24 h later). These results show for the first time that hrIL-1ra blocks PGE2, IL-1 alpha and IL-1 beta but not alkaline phosphatase activity, which is a marker in growing bone and in calcific and inflamed tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism*
  • Animals
  • Chronic Disease
  • Dinoprostone / antagonists & inhibitors*
  • Dinoprostone / biosynthesis
  • Enzyme-Linked Immunosorbent Assay
  • Granuloma / chemically induced
  • Granuloma / enzymology*
  • Granuloma / pathology
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / pharmacology*
  • Lipopolysaccharides / immunology
  • Male
  • Mice
  • Potassium Permanganate
  • Radioimmunoassay
  • Recombinant Proteins / pharmacology
  • Sialoglycoproteins / pharmacology*
  • Skin Diseases / chemically induced
  • Skin Diseases / enzymology*
  • Skin Diseases / pathology

Substances

  • IL1RN protein, human
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Lipopolysaccharides
  • Recombinant Proteins
  • Sialoglycoproteins
  • Potassium Permanganate
  • Alkaline Phosphatase
  • Dinoprostone