Cytokines and IDDM: implications for etiology and therapy

The evidence that human insulin-dependent diabetes mellitus (IDDM) is a T cell-mediated disease is well substantiated, and the use of transgenic technology to understand the Th1/Th2 paradigm will provide keys to attenuating pathogenic autoimmunity. Insofar as the role of Th1 cytokines in IDDM is concerned, interferon gamma is considered a critical player in the etiology, a proinflammatory role has been determined for IDDM, interleukin-2 is considered an "amplification" factor, and tumor necrosis factor-alpha presents dichotomous effects. Regarding the role of Th2 cytokines in IDDM, interleukin-4 is essential for immunoprotection and counterregulation of IDDM, and interleukin-10 plays immunoprotective and destructive roles. Therefore, Th1 and Th2 cytokines, when expressed individually in islets of Langerhans, have provided surprising results in manipulating the IDDM of transgenic NOD mice. The current data show that the same cytokine can produce either protective or pathological effects, depending upon the timing of its participation in the disease process. Of all the cytokines examined, IL-4 seems to be the likely candidate for preventing IDDM.