INTERLEUKIN-12 - A POTENTIAL LINK BETWEEN NERVE-CELLS AND THE IMMUNE-RESPONSE IN INFLAMMATORY DISORDERS

Background: The nervous system has been implicated in several inflammatory skin disorders based on evidence such as the role of stress in inducing lesions, symmetry of lesions, and sparing of denervated skin. Interleukin 12 (IL-12) is a cytokine recently shown to promote cellular immune responses characterized by delayed-type hypersensitivity and production of the TH1-lymphokine, interferon-gamma. Materials and Methods: Using immunohistochemistry, IL-12 immunoreactivity was identified in cryostat sections of normal and diseased human skin samples, and in the peripheral and central nervous system of rodents and human tissue samples. IL-12 p35 and p40 mRNAs were detected using reverse transcriptase-polymerase chain reaction in tissue samples and cultured cells. IL-12 protein levels were also examined by ELISA and quantitative bioassay utilizing an IL-12-dependent cell line. Results: By immunostaining IL-12 was detected in free nerve ending in the epidermis of normal and diseased skin samples, and also in the dermal nerve fibers. Strong reactivity was detected in axonal processes and in various glial cell types. In addition, IL-12 protein and mRNA were contained within cutaneous peripheral nerves and spinal cord tissues, and functional levels of IL-12 were produced by cultured Schwann cells. Conclusions: It is likely that IL-12 is important in initiating or propagating selected inflammatory skin lesions and in determining the pattern of disease that will develop. The presence of IL-12 in neural tissue suggests a mechanism whereby the nervous system can modify or amplify cutaneous and perhaps other immune responses.