A therapeutic trial of experimental tuberculosis with gamma-interferon in an immunocompromised mouse model

Abstract

It has been well documented that IFN-gamma plays an important role in the host defense against Mycobacterium tuberculosis infection through activating macrophages to kill the organism. In the present study, we studied the effects of in vivo injection of monoclonal antibody against IFN-gamma (anti-IFN-gamma mAb) on the mycobacterial infection to confirm the role of this cytokine. The injection of anti-IFN-gamma mAb suppressed the enhanced expression of MHC class II and ICAM-1 on pulmonary parenchymal macrophages induced by intravenous injection of Mycobacterium bovis BCG. The number of bacilli recovered from lung of mice treated with anti-IFN-gamma mAb and injected with Mycobacterium tuberculosis H37Rv was significantly larger than that of the control infected mice. From these results, it was indicated that anti-IFN-gamma mAb blocked the activities of endogenously synthesized IFN-gamma, thus inhibited the activation of macrophages to kill the bacilli. Next, CD4+ T cell-depleted mice were prepared by injecting anti-CD4 mAb and used as immunocompromised animal. When infected with M. tuberculosis, the multiplication of the bacilli within the lungs of such immunocompromised mice was much more enhanced in comparison with the control mice with intact CD4+ T cells. Administration of IFN-gamma significantly reduced the number of the bacilli in lung. Further, in an in vitro study with human lung macrophages, IFN-gamma enhanced the killing activity of macrophages against M. tuberculosis in a dose dependent manner, and suboptimal dose of 1 alpha, 25-dihydroxyvitamin D3 synergistically augmented the effect of IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)