Mechanisms of Antagonism of Interleukin-1α by Synthetic Interleukin-1 Blockers

ABSTRACT

A series of interleukin-1 blockers, CK-compounds, were shown to inhibit the dose-response curve of IL-1 induced uveitis in a non-competitive manner. CK-compounds showed little or weak effects on PGE₂ production, leukocyte chemotaxis, and lipoxygenase activity which were markedly inhibited by indomethacin, REV 9501, and NDGA, respectively. These results indicate that CK-compounds do not fall into the conventional class of non-steroidal arachidonate mediated antiinflammatory agents. CK-compounds should therefore be classified as novel compounds to block IL-1 non-competitively and belong to non-steroidal, non-arachidonate mediated anti-inflammatory agents.