Expression and correlation of TGF-beta1, iNOS, IFN-gamma, and IL-10 mRNA in borderline lepromatous leprosy lesions before and after treatment

Shin, Jeong Hyun; Choi, Hae Young; Myung, Ki Bum; Cho, Sang Nae

Abstract

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae, which is an obligate intracelluar pathogen. It presents broad spectrum of clinical manifestations depending on the host's specific cell-mediated immune response to M. leprae. Especially, type I Th cells and macrophages are important in defense mechanism to M. leprae, and the immune response is regulated by cytokines secreted by immune cells. Recent investigations showed nitric oxide(NO) was the key molecule in the killing activity of macrophages, which was enhanced by IFN-gamma but suppressed by TGF-beta1 and IL-10. Since cytokine is secreted by activated immune cells with antigenic stimulation, decreased antigens by treatment modulates the expression of cytokines in leprosy. In this study, we observed the dynamics of cytokines expression using RT-PCR, such as TGF-beta1 and IL-10, which suppress the activity of macrophages, IFN-gamma, which activates macrophages, and iNOS, which represents the killing activity of macrophages, in the lesions taken from fifteen borderline lepromatous leprosy patients before and after multiple drug therapy for 4 weeks. The results are summarized as follows: 1. Before treatment, cytokines were expressed in order of IL-10, iNOS, TGF-beta1 and IFN-gamma(p>0.05). 2. After 4 weeks treatment, cytokines were expressed in order of iNOS, IL-10, TGF-beta1 and IFN-gamma(p<0.05). 3. Fifty-four percent of patients showed a non-polarized Th 0 pattern, 33% a polarized Th 1 pattern, and 20% Th-negative. Th 2 pattern was not observed. 4. The changes of cytokines expression after 4 weeks treatment were not significant, although mRNA of IL-10, TGF-beta1 and IFN-gamma were somewhat decreased. 5. There was negative correlation between TGF-beta1 and iNOS(gamma(2)=0.499, p<0.05, before treatment), positive correlation between TGF-beta1 and IFN-gamma(gamma(2)= 0.622, p<0.05, before treatment), and positive correlation between IFN-gamma and IL-10(gamma(2)= 0.935, p<0.05, before treatment; gamma(2)= 0.937, p<0.05, after treatment). In conclusion, these results suggest that TGF-beta1 and IL-10 may contribute to immune suppression in multibacterial leprosy patients, and that TGF-beta1 suppresses iNOS expression in macrophages. With 4 weeks treatment, the significant changes in cytokines expression were not observed. Interestingly, the majority of BL patients showed Th 0 pattern of cytokine, and none of Th 2 pattern.