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 ng/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-1beta (0.1-10 ng/ml). In addition, we show that hrIL-1ra (250 ng/ml) strongly inhibited IL-1alpha and IL-1bbeta, as measured by ELISA method, in the minced granuloma tissue treated overnight with LPS 1 mug/ml or IL-1beta (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 mug/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-1alpha and IL-1beta but not alkaline phosphatase activity, which is a marker in growing bone and in calcific and inflamed tissue.