Reversal of ultraviolet radiation-induced immune suppression by recombinant interleukin-12: suppression of cytokine production.
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.
Schmitt
D A
DA
Department of Immunology, The University of Texas M.D. Anderson Cancer Center, and the Graduate School for Biomedical Sciences, Houston, TX 77030, USA.
Walterscheid
J P
JP
Ullrich
S E
SE
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007108:Immune Tolerance / Q000276:immunology / Q000528:radiation effects*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000276:immunology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014466:Ultraviolet Rays
D016207:Cytokines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma