CINNAMALDEHYDE INHIBITS LYMPHOCYTE-PROLIFERATION AND MODULATES T-CELLDIFFERENTIATION

Two kinds of cinnamaldehyde derivative, 2'-hydroxycinnamaldehyde (HCA) and 2'-benzoxycinnamaldehyde (BCA), were studied for their immunomodu latory effects. These compounds were screened as anticancer drug candi dates from stem bark of Cinnamomum cassia for their inhibitory effect on farnesyl protein transferase activity. Ras activation, which is acc ompanied with its farnesylation, has been known to be important in imm une cell activation as well as in carcinogenesis; Treatment of these c innamaldehydes to mouse splenocyte cultures induced suppression of lym phoproliferation following both Con A and LPS stimulation in a dose-de pendent manner. A dose of 1 mu M of HCA and BCA inhibited the Con A-st imulated proliferation by 69% and 60%, and the LPS-induced proliferati on by 29% and 21%, respectively. However, the proliferation induced by PMA plus ionomycin was affected by neither HCA nor BCA treatment. Dec reased levels of antibody production by HCA or BCA treatment were obse rved in both SRBC-immunized mice and LPS-stimulated splenocyte culture s. The exposure of thymocytes to HCA or BCA for 48 h accelerated T-cel l differentiation from CD4 and CD8 double positive cells to CD4 or CD8 single positive cells. The inhibitory effect of cinnamaldehyde on lym phoproliferation was specific to the early phase of cell activation, s howing the strongest inhibition of Con A- or LPS-stimulated proliferat ion when added concomitantly with the mitogens. In addition, the treat ment of HCA and BCA to splenocyte cultures attenuated the Con A-trigge red progression of cell cycle at G(1) phase with no inhibition of S to G(2)/M phase transition. Although cinnamaldehyde treatment had no eff ect on the IL-2 production by splenocyte cultures stimulated with Con A, it inhibited markedly and dose-dependently the expression of IL-2R alpha and interferon-gamma. Taken together, the results in this study suggest both HCA and BCA inhibit the lymphoproliferation and induce a T-cell differentiation through the blockade of early steps in signalin g pathway leading to cell growth. (C) 1998 International Society for I mmunopharmacology. Published by Elsevier Science Ltd.