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Reversal of ultraviolet radiation‐induced immune suppression by recombinant interleukin‐12: suppression of cytokine production
Author(s) -
Schmitt D. A.,
Walterscheid J. P.,
Ullrich S. E.
Publication year - 2000
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2000.00084.x
Subject(s) - immune system , cytokine , secretion , tumor necrosis factor alpha , biology , lymphokine , immunology , interleukin 4 , interleukin , cancer research , endocrinology
Summary 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‐γ (IFN‐γ) 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‐γ 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‐α (TNF‐α) production. Because IL‐10 is involved in the UV‐induced suppression of delayed‐type hypersensitivity and TNF‐α 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.