Thiol-containing compounds inhibit the production of monocyte/macrophage-derived angiogenic activity

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Abstract
Macrophage (Mø)-mediated angiogenesis is believed to play an important role in the pathogenesis of rheumatoid arthritis. Gold sodium thiomalate, which is used in the treatment of rheumatoid arthritis, is a potent inhibitor of the production of mø-derived angiogenic activity. To determine the mechanism of this inhibition, we studied the effects of thiol containing compounds (TCCs) on elicited mouse peritoneal møs and lipopolysaccharide stimulated normal human monocytes. Monocyte/mø conditioned media were potently angiogenic when assayed in rat corneas, while conditioned media from viable monocyte/møs treated with TCCs (at concentrations of 8.3–16.6×10−5M) were not. TCCs inhibited production of angiogenic activity by the møs rather than affecting other components of the angiogenic response such as the angiogenic factors or the target microvasculature of the rat cornea. Levels of the angiogenic mediator tumor necrosis factor-alpha (TNF-alpha) were not decreased in conditioned media of monocyte/møs treated with TCCs. We conclude that TCCs are potent inhibitors of the production of mø-mediated angiogenic activity. This action of TCCs on møs may be in part responsible for the mechanism of action of therapeutic gold compounds in rheumatoid arthritis.