Arginine modulated cyclosporine-induced immune suppression in rats transplanted with gastric cancer cells.
BACKGROUND
The incidence of cancer is significantly increased in kidney transplant patients receiving cyclosporine treatment. It has been reported that arginine can modify cyclosporine-induced nephrotoxicity in rats. Whether arginine interfered with cyclosporine-induced immune suppression in tumor transplant is not clear.


METHODS
Male Wistar rats were inoculated subcutaneously with human gastric cancer SC-M1 cells and separated into 4 groups; control, cyclosporine, cyclosporine plus arginine and cyclosporine plus glycine groups. The growth of SC-M1 tumor was monitored on 4, 7, 10, 14 and 21 days after tumor implant. In another set of experiments, the rats were separated into control, cyclosporine, arginine and cyclosporine plus arginine groups. After treatment for one week, mononuclear cells were collected and stained with anti-rat CD3 antibody followed by flowcytometric analysis. On the other hand, splenocytes from each group of rats were stimulated with phyto-hemaglutinin (PHA) to determine their DNA synthesis by 3H-thymidine uptake assay.


RESULTS
The SC-M1 tumors in the cyclosporine-treated rats were larger than that of the arginine plus cyclosporine group. Although SC-M1 tumors were eventually rejected in Wistar rats, the duration of detectable SC-M1 tumors in cyclosporine-treated rats was longer than that of rats treated with arginine plus cyclosporine. More infiltrating inflammatory cells were detected at an early stage of tumor rejection in rats treated with arginine plus cyclosporine than in cyclosporine-treated rats. In vitro analysis of PHA-stimulated splenocyte proliferation showed that arginine activated lymphocyte proliferation while cyclosporine inhibited lymphocyte proliferation. Arginine significantly interfered with cyclosporine-induced growth inhibition of PHA stimulated lymphocytes (p = 0.0039).


CONCLUSIONS
Using a tumor transplant model, we have found that dietary supplements of arginine interfered with cyclosporine-induced immunosuppression in rats. The antagonistic effect between arginine and cyclosporine on immune suppression is worthy of further investigation in organ transplant patients.
Kung
S P
SP
Department of Surgery, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C. spkung@vghtpe.gov.tw
Wu
C W
CW
Lui
W Y
WY
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014407:Tumor Cells, Cultured
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001120:Arginine