[Factors for the onset of and the exacerbation of tuberculosis. 2. Host factors promoting the occurrence and exacerbation of tuberculosis: significance of Th1-Th2 cytokine balance].

The problem of tuberculosis is emerging again with increase in the population of aged people and immunocompromised patients in Japan. It has been well documented that cell-mediated immunity play a central role in host resistance to infection with Mycobacterium tuberculosis. A decade years ago, Mosmann et al. found that helper T (Th) cells are divided into two subsets, Th1 and Th2, based on the cytokines which they produce. Th1 cells produce IFN-gamma, while Th2 cells secrete IL-4, IL-10 and IL-13. Many recent studies have provided evidences suggesting that the Th1-Th2 cytokine balance may determine the outcome of some diseases. For example, predominant production of Th1 cytokines may prevent the occurrence of infectious diseases caused by intracellularly growing pathogens and Th2 cytokines may be involved in the exacerbation of allergic diseases. On the other hand, IL-12 plays an essential role in the differentiation of Th1 cells from naive T cells, and IL-18 potentiates this effect although it does not show such effect by itself. In the present study, we examined the role for these two cytokines in host resistance to mycobacterial infection by using an animal model with either IL-12 or IL-18 gene-disrupted mice. The organ loads of this pathogen in lung, liver and spleen were significantly larger in these gene-disrupted mice than those in control mice. There are several host factors which determines the outcome of mycobacterial infection. Among them, steroid treatment and AIDS are important factors. In this study, we determined the effect of these pathological conditions on Th1-Th2 cytokine balance and outcome of mycobacterial infection using murine models. In both conditions, the exacerbated infection was well correlated with the reduced production of IFN-gamma. Furthermore, I also discussed about the relationship between other host factors and balance in the production of Th1 and Th2 cytokines.