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

Background: The nervous system has been implicated in several inflamma tory skin disorders based on evidence such as the role of stress in in ducing lesions, symmetry of lesions, and sparing of denervated skin. I nterleukin 12 (IL-12) is a cytokine recently shown to promote cellular immune responses characterized by delayed-type hypersensitivity and p roduction of the TH1-lymphokine, interferon-gamma. Materials and Metho ds: 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 transcri ptase-polymerase chain reaction in tissue samples and cultured cells. IL-12 protein levels were also examined by ELISA and quantitative bioa ssay utilizing an IL-12-dependent cell line. Results: By immunostainin g IL-12 was detected in free nerve ending in the epidermis of normal a nd 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 cutan eous peripheral nerves and spinal cord tissues, and functional levels of IL-12 were produced by cultured Schwann cells. Conclusions: It is l ikely that IL-12 is important in initiating or propagating selected in flammatory skin lesions and in determining the pattern of disease that will develop. The presence of IL-12 in neural tissue suggests a mecha nism whereby the nervous system can modify or amplify cutaneous and pe rhaps other immune responses.