Suppression of humoral immune response to hepatitis B surface antigen vaccine in BALB/c mice by 1-methyl-tryptophan co-administration.

BACKGROUND AND THE PURPOSE OF THE STUDY: Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immune response. The purpose of this study was to determine the effect of the IDO inhibitor namely 1-methyl-DL-tryptophan (DL-1-MT) on antibody production after vaccination with hepatitis B surface (HBs) antigen. METHODS: Four groups of BALB/c mice were immunized with a HBs antigen vaccine. In the first group the vaccine had no DL-1-MT, whereas in the other three groups the vaccine contained 1 mg, 10 mg and 20 mg DL-1-MT. Blood samples were collected 5 weeks post-vaccination and anti-HBs antibodies in the serum were measured by ELISA. RESULTS: Compared to the three groups of mice that were immunized with the vaccines containing DL-1-MT, serum anti-HBs level was much higher in the mice that were immunized with the vaccine with out DL-1-MT. CONCLUSIONS: Inhibition of IDO at the time of vaccination decreased humoral immune response to HBs antigen vaccine. The idea that IDO activity is simply immunosuppressive may need to be re-evaluated.

L-arginine supplementation does not affect chemically induced carcinogenesis and tumor growth in BALB-c mice.

UNLABELLED: T-cell zeta-chain downregulation is common in various types of cancer and it is proposed as a mechanism of cancer immunosubversion. L-arginine consumption by arginase rich suppressor myeloid cells has been incriminated. The effect of L-arginine supplementation on chemically induced carcinogenesis and tumor growth in mice was evaluated. METHODS: Eight-week old female BALB-c mice were used. Ten mice were injected i.m. with 0.6 mg methylcholanthrene (MCA) once. Ten mice were injected with MCA once and were receiving L-arginine supplementation (5% in animal drinking water) continuously during the study. Mice with cancer were sacrificed 12 weeks after. RESULTS: From the 10 MCA injected mice 6 developed sarcoma. From the 10 MCA injected mice that were receiving L-arginine supplementation 7 developed sarcoma. L-arginine supplementation did not affect MCA induced carcinogenesis (p=1.0, Fisher's exact test). The weight of tumors was not different between the tumors derived from mice that were or were not receiving L-arginine supplementation (1088.3+/-590.2 mg vs. 969.6+/-608.1 mg respectively, p=0.729, unpaired t-test). CONCLUSION: L-arginine supplementation does not affect chemically induced carcinogenesis and tumor growth in BALB-c mice. Although zeta-chain downregulation could be a mechanism of cancer immunosubversion there are enough other cancer immunosubversion mechanisms that were not overwhelmed by L-arginine supplementation. Additionally, except cancer immunosubversion, cancer immunoselection is another, possibly more significant, mechanism of tumor escape from immunosurveillance.