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  • Title: Reversal of ultraviolet radiation-induced immune suppression by recombinant interleukin-12: suppression of cytokine production.
    Author: Schmitt DA, Walterscheid JP, Ullrich SE.
    Journal: Immunology; 2000 Sep; 101(1):90-6. PubMed ID: 11012758.
    Abstract:
    Exposure to ultraviolet (UV) radiation, a complete carcinogen, suppresses the immune response. Data from a number of laboratories have indicated that one consequence of UV exposure is suppressed T helper type 1 (Th1) cell function with normal Th2 cell activation, resulting in a shift to a Th2-like phenotype. The reversal of UV-induced immune suppression and tolerance induction by recombinant interleukin-12 (rIL-12) supports this observation. The focus of this study was to determine the mechanism(s) by which rIL-12 reverses UV-induced immune suppression. Two possibilities were considered: up-regulation of interferon-gamma (IFN-gamma) secretion by rIL-12 and suppression of UV-induced cytokine secretion by rIL-12. To our surprise we found that the ability of rIL-12 to overcome UV-induced immune suppression was independent of its ability to up-regulate IFN-gamma secretion. Rather, rIL-12 suppressed the production of cytokines that are known to be important in UV-induced immune suppression. Injecting UV-irradiated mice with rIL-12, or adding rIL-12 to UV-irradiated keratinocyte cultures suppressed IL-10 secretion, in part by affecting the transcription of the IL-10 gene. Furthermore, we found that rIL-12 suppressed UV-induced tumour necrosis factor-alpha (TNF-alpha) production. Because IL-10 is involved in the UV-induced suppression of delayed-type hypersensitivity and TNF-alpha in the UV-induced suppression of contact allergy, these findings provide a mechanism to explain how rIL-12 overcomes UV-induced immune suppression in these related but different immune reactions. In addition, they suggest a novel mechanism by which rIL-12 alters immune reactivity, direct suppression of cytokine secretion induced by UV radiation.
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