Mechanisms of antagonism of interleukin-1 alpha by synthetic interleukin-1 blockers.

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 anti-inflammatory 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.