Pharmacological properties of E5090, an orally active inhibitor of IL-1 generation.

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E5090 is a newly synthesized orally active inhibitor of IL-1 generation without cyclooxygenase inhibiting activity form. Orally administered E5090 is rapidly changed to the pharmacologically active, DA-E5090, by deacetylation. On the in vitro systems using human monocytes and rats peritoneal macrophages stimulated with LPS, DA-E5090 dose-dependently inhibited the IL-1 generation due to the inhibition of IL-1mRNA expression. On the in vivo systems of IL-1 generation in rat air-pouch models induced by nonallergic or allergic stimuli, orally administered E5090 dose-dependently inhibited the generation of IL-1 activity and the chronic granuloma formation similar to steroidal anti-inflammatory drug, prednisolone. On the other hand, indomethacin had no effects on both IL-1 generation and granuloma formaton in spite of the perfect inhibition of prostaglandin E2 generation. The quantitative measurements of other inflammatory cytokines such as TNF and IL-6 suggest that IL-1 may be a main mediator for granuloma formation in these animal models. In adjuvant arthritis, E5090 suppressed not only the paw inflammation but also the in creases in ESR and peripheral blood leucocyte numbers, being similar to prednisolone in these respects, but different from indomethacin. These results suggest that the inhibitor of IL-1 generation may show steroid-like anti-inflammatory effects.
日本炎症・再生医学会の論文