Interleukin-12 Prevents Ultraviolet B-Induced Local Immunosuppression and Overcomes UVB-Induced Tolerance

Abstract

Ultraviolet (UV) light abrogates contact hypersensitivity (CHS) responses and induces hapten-specific tolerance. Because Th-1 cells are critically involved in CHS and are induced to develop by the cytokine interleukin (IL)-12, we asked whether IL-12 might overcome UV-induced local immunosuppression. C3H/HeN mice exposed to low doses of UV light over 4 d and hapten sensitized through the irradiated skin area with dinitrofluorobenzene showed profound inhibition of the CHS response, which was completely prevented upon intraperitoneal injection of murine recombinant IL-12 (rIL-12) after the last UV exposure. UV-treated mice resensitized 14 d after the first challenge displayed hapten-specific tolerance, whereas UV-exposed mice injected with rIL-12 before the first sensitization exhibited a vigorous CHS response. Furthermore, mice that were initially sensitized through UV-exposed skin also produced a significant CHS reaction when they received rIL-12 before resensitization. Adoptive transfer of spleen and lymph node cells from UV-irradiated mice treated with rIL-12 had no effect on the CHS response in recipient mice, whereas transfer of cells from UV-treated mice inhibited the immune response. These findings demonstrate that rIL-12 can prevent UV-induced local immunosuppression and overcome UV-induced hapten-specific tolerance.

IL-18 Reduces Ultraviolet Radiation-Induced DNA Damage and Thereby Affects Photoimmunosuppression

“…In addition, IL-12 exerts the capacity to even break established immunotolerance. Injection of IL-12 into UV-tolerized mice enables sensitization with the hapten to which the mice had been tolerized (19,20). Accordingly, IL-12 inhibits the suppressive activity of UV-induced regulatory T cells as demonstrated in adoptive transfer studies.…”

The pathophysiology of photosensitivity in lupus erythematosus

“…Acute low-dose UVA administration, but not UVB, also results in IL-12 production by keratinocytes (231,232). IL-12 is a potent immunostimulant that can abrogate tolerance induced by low dose UVB (233).…”

Photoprotection of natural flavonoids

“…IL-10 appears to be a key mediator of UV radiation-induced immunosuppression (Loser et al, 2007). In contrast to the effects of IL-10, interleukin-12 (IL-12) prevents UVB radiation-induced local immunosuppression (Schwarz et al, 1996). Importantly, IL-12 was found to accelerate the removal of UV-induced DNA lesions in keratinocytes by inducing nucleotide-excision repair, strongly suggesting that it plays a protective role in photocarcinogenesis of the skin (Schwarz et al, 2002).…”