SHIH-HUA FANG¹*, YU-CHI HOU², SU-LAN HSIU³ AND PEI-DAWN LEE CHAO³

^1. Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan, R.O.C.
^2. School of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
^3. School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.

(Received: October 21, 2005; Accepted: January 18, 2006)

(Received: October 21, 2005; Accepted: January 18, 2006)

Abstract

   A previous study indicated that the coadministration of decoction of Citri Grandis Pericarpium (CGP), the peels of Citrus grandis (Rutaceae), significantly increased the blood level of cyclosporin (CsA) and resulted in acute intoxication of pigs.  In this study, we aimed to measure the effects of CGP on the distribution of CsA in both lymphoid and non-lymphoid tissues as well as on the immune cell function in mice.  Our results showed that coadministration of 3 g/kg CGP with CsA (Neoral^®, 10 mg/kg) significantly decreased the concentrations of CsA in blood, liver, kidney and spleen by 37 %, 45 %, 46 % and 51 %, respectively, after a two week treatment. The decrease in CsA level correlated positively with the CGP dose.  Pharmadynamically, coadministration of CGP restored the phagocytosis activity in blood decreased by CsA.  Moreover, the nitric oxide production of activated macrophages and helper T cell type 1 (Th1) cytokines production suppressed by CsA were also reversed by the coadministration of CGP.  In conclusion, coadministration of CGP significantly decreased the systemic exposure of CsA and resulted in higher macrophage and Th1 type activities than giving CsA alone in mice.  Therefore, the combined use of CGP with CsA requires close monitoring clinically.

Key words: Citrus grandis, cyclosporin, immune response, Th1/Th2 cytokines