Promising immunotherapies with Th1-related cytokines against infectious diseases.

In recent years, there has been an increase in the number of individuals with compromised immune systems. This is due to the rise in the numbers of aging people, patients receiving immunosuppressive treatment after organ transplantation, patients with hematological malignancies, and patients with AIDS. These individuals frequently fall into helper T cell (Th)1-Th2 cytokine imbalance due to a shift towards a Th2-dominant condition. Such a pathological condition puts them at a high risk for developing infectious diseases caused by a variety of microbial pathogens which are often refractory to conventional chemotherapy. Therefore, the administration of Th1-related cytokines is expected to be promising immunotherapy against these intractable infectious diseases. In a series of investigations, we have demonstrated the effectiveness of treatment with Th1-related cytokines, such as interferon (IFN)-gamma, interleukin (IL)-12, and IL-18, in protecting animals from experimental infectious diseases caused by Mycobacterium tuberculosis and Cryptococcus neoformans. Recently, several investigators reported successful clinical treatment with IFN-gamma or IL-12 in patients with intractable tuberculous and nontuberculous mycobacteriosis. Thus, now is an appropriate time for scientific evaluation to clinically confirm the effectiveness of these novel immunotherapies.