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.
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.
Conti
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P
Immunology Division, Institute of Experimental Medicine, University of Chieti Medical School, Italy.
Barbacane
R C
RC
Felaco
M
M
Grilli
A
A
Placido
F C
FC
Reale
M
M
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D002908:Chronic Disease; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006099:Granuloma / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D011196:Potassium Permanganate; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D012871:Skin Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology
C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D011196:Potassium Permanganate; D000469:Alkaline Phosphatase; D015232:Dinoprostone