Contributing factors to the pathobiology of asthma - The Th1/Th2 paradigm

CD4+ "helper" T-lymphocytes in murine and human models have been divided in to Th1 and Th2 subclasses, characterized by the profile of cytokines they s ecrete: INF-gamma (and perhaps IL-2 and TNF-beta) by Th1 cells, and IL-4 (a nd perhaps IL-5, IL6, IL-10, and IL-13) by Th2 cells. Although a strict div ision into Th1 and Th2 phenotypes in humans (unlike murine systems) may not be possible, the asthmatic diathesis in humans appears to be one largely c haracterized by inflammatory responses associated with Th2 cells and their cytokines particularly IL-4, IL-13, and IL-5. Other pulmonary disorders, su ch as those associated with infectious diseases including tuberculosis, app ear to favor an immunologic response characteristic of Th1-cells, and its d efining cytokine IFN-gamma. This apparent Th1/Th2 immune dysregulation in a sthma is an area of active investigation and forms the basis for ongoing at tempts to change this phenotype through a variety of approaches. These incl ude immunotherapy with conventional antigens, designer peptides, oligonucle otides, and anti-IgE, and pharmacotherapy with immune modulating drugs, cyt okines, cytokine agonists and cytokine antagonists, and antibodies. This fi eld of investigation promises to usher in a whole new approach to our under standing of asthma and ways to approach its treatment.