Cinnamaldehyde inhibits lymphocyte proliferation and modulates T-cell differentiation

Two kinds of cinnamaldehyde derivative, 2'-hydroxycinnamaldehyde (HCA) and 2'-benzoxycinnamaldehyde (BCA), were studied for their immunomodulatory effects. These compounds were screened as anticancer drug candidates from stem bark of Cinnamomum cassia for their inhibitory effect on farnesyl protein transferase activity. Ras activation, which is accompanied with its farnesylation, has been known to be important in immune cell activation as well as in carcinogenesis; Treatment of these cinnamaldehydes to mouse splenocyte cultures induced suppression of lymphoproliferation following both Con A and LPS stimulation in a dose-dependent manner. A dose of 1 mu M of HCA and BCA inhibited the Con A-stimulated proliferation by 69% and 60%, and the LPS-induced proliferation by 29% and 21%, respectively. However, the proliferation induced by PMA plus ionomycin was affected by neither HCA nor BCA treatment. Decreased levels of antibody production by HCA or BCA treatment were observed in both SRBC-immunized mice and LPS-stimulated splenocyte cultures. The exposure of thymocytes to HCA or BCA for 48 h accelerated T-cell differentiation from CD4 and CD8 double positive cells to CD4 or CD8 single positive cells. The inhibitory effect of cinnamaldehyde on lymphoproliferation was specific to the early phase of cell activation, showing the strongest inhibition of Con A- or LPS-stimulated proliferation when added concomitantly with the mitogens. In addition, the treatment of HCA and BCA to splenocyte cultures attenuated the Con A-triggered progression of cell cycle at G(1) phase with no inhibition of S to G(2)/M phase transition. Although cinnamaldehyde treatment had no effect 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 signaling pathway leading to cell growth. (C) 1998 International Society for Immunopharmacology. Published by Elsevier Science Ltd.