3-Deazaadenosine--an inhibitor of interleukin 1 production by human peripheral blood monocytes

3-Deazaadenosine (c3Ado) has been reported to have properties of an immunosuppressive and anti-inflammatory agent. This study was designed to investigate whether c3Ado might exert anti-inflammatory activities through inhibiting Interleukin 1 (IL-1). c3Ado was found to be a potent inhibitor of IL-1 production by LPS stimulated human peripheral blood monocytes and acted at the level of synthesis rather than secretion. c3Ado also had direct effects on IL-1 biological activity in two separate assays; thymocyte proliferation and induction of prostaglandin release. Further experiments indicated that c3Ado also inhibited growth factor dependent proliferation driven by both Interleukin-2 and Interleukin-3 as well as the proliferation of a number of non-growth factor dependent cells. However, short term exposure to c3Ado resulted in no inhibition of 3H-thymidine incorporation by cells but a significant inhibition of 3H-uridine uptake into TCA precipitable material. These results suggest that c3Ado is a selective inhibitor of RNA synthesis and inhibits IL-1 production and activity by blocking new messenger RNA production induced by LPS or IL-1. General inhibition of RNA synthesis would also account for its anti-proliferative activity.