INHIBITORY-ACTION OF TRANILAST, AN ANTIALLERGIC DRUG, ON THE RELEASE OF CYTOKINES AND PGE(2) FROM HUMAN MONOCYTES-MACROPHAGES

Tranilast, an anti-allergic drug that inhibits the release of substances such as histamine and prostaglandins from mast cells, has been reported to improve keloids and hypertrophic scars which originate from the abnormal proliferation and excessive collagen accumulation of fibroblasts. It has been considered that various chemical mediators produced by inflammatory cells play important roles in the development of keloids and hypertrophic scars. We therefore studied the effect of tranilast on the release of chemical mediators including transforming growth factor (TGF)-beta1, interleukin (IL)-1beta and prostaglandin (PG) E2 which are produced by the human monocytes-macrophages, and estimated whether these mediators induce collagen synthesis and cell proliferation of normal skin fibroblasts. Tranilast inhibited the release of TGF-beta1, IL- 1beta and PGE2 from the human monocytes-macrophages. TGF-beta1 (25-200 pM) enhanced the collagen synthesis by fibroblasts. IL-1 (0.1-1 U/ml) increased the proliferation and conversely decreased the collagen synthesis. PGE2 (2 mug/ml) enhanced the collagen synthesis. These results suggest that tranilast suppresses collagen synthesis by fibroblasts through inhibiting TGF-beta1 and PGE2 production and cell proliferation by fibroblasts through inhibiting IL-1 production by inflammatory cells such as macrophages.