UV-induced DNA damage has been recognized as the major molecular trigger for photoimmunosuppression.
IL-12 prevents UV-induced immunosuppression via its recently discovered capacity to reduce DNA damage presumably via induction of DNA repair. Because
IL-18 shares some biological activities with
IL-12 we studied the effect of
IL-18 on UV-induced DNA damage and immunosuppression.
IL-18 reduced UV-induced apoptosis of keratinocytes and supported long-term cell survival on UV exposure. Injection of
IL-18 into mice that were exposed to UV radiation significantly lowered the number of apoptotic keratinocytes. Accordingly, radiation immunohistochemistry revealed reduced amounts of DNA damage in epidermal cells upon injection of
IL-18. These effects were not observed in
DNA repair-deficient (XpaKO) mice, indicating that
IL-18 like
IL-12 reduces DNA damage via DNA repair. UV-mediated suppression of the induction of
contact hypersensitivity, which is known to be primarily triggered by DNA damage, was prevented upon injection of
IL-18 before UV exposure in wild-type but not in XpaKO mice. In contrast to
IL-12,
IL-18 was not able either in wild-type or in XpaKO mice to break UV-induced immunotolerance that is mediated via regulatory T cells rather than in
a DNA damage-dependent fashion. This result indicates that
IL-12 is still unique in its capacity to restore immune responses because of its effect on regulatory T cells. Together, these data identify
IL-18 as a further
cytokine that exhibits the capacity to affect DNA repair. Though being primarily a proinflammatory
cytokine through this capacity,
IL-18 can also foster an immune response that is suppressed by UV radiation.