We have shown previously that
silymarin, a plant
flavonoid, inhibits UVB-induced photocarcinogenesis in mice. As UVB-induced immunosuppression has been implicated in the development of
skin cancer, we investigated whether
silymarin can modulate the effects of UVB radiation on the immune system. Treatment of C3H/HeN mice with topically applied
silymarin (0.5 or 1.0 mg/cm(2)) or
silibinin, a major component of
silymarin, markedly inhibited UVB (180 mJ/cm(2))-induced suppression of
contact hypersensitivity response in a local model of immunosuppression and had a moderate inhibitory effect in a systemic model of
contact hypersensitivity.
Silymarin reduced the UVB-induced enhancement of the levels of the immunosuppressive
cytokine,
interleukin (IL)-10, in the skin and draining lymph nodes and enhanced the levels of the immunostimulatory
cytokine,
IL-12.
Intraperitoneal injection of mice treated with
silymarin with an
endotoxin-free neutralizing anti-IL-12 antibody abrogated the protective effects of the
silymarin against UVB-induced suppression of the
contact hypersensitivity response. Furthermore, the treatment of
silymarin did not prevent UVB-induced suppression of the
contact hypersensitivity response in
IL-12 knockout mice but prevented it in their wild-type mice. Moreover, i.p. injection of
IL-12 to
silymarin-treated or non-
silymarin-treated
IL-12 knockout mice resulted in an enhanced response to
contact hypersensitivity compared with the response in mice that were exposed to either UVB alone or
silymarin plus UVB. These data indicate for the first time that
silymarin has the ability to protect mice from UVB-induced immunosuppression and that this protective effect is mediated, at least in part, through
IL-12.