HISTAMINE ENHANCES UVB-INDUCED IL-6 PRODUCTION BY HUMAN KERATINOCYTES

Histamine, an important mediator in immediate-type hypersensitivity, i s elevated in the skin of patients with atopic dermatitis and is consi dered to play a pathogenic role in atopic dermatitis. In this study, t o elucidate the mechanism of sun exposure-induced exacerbation of skin lesions in atopic dermatitis, we examined the effect of histamine on proinflammatory cytokine production of keratinocytes induced by ultrav iolet (UV) B irradiation. Cultured human keratinocytes were irradiated with 30 mJ/cm(2) of UVB and incubated with histamine over the concent ration range 10(-7) to 10(-4) M, and the IL-1 alpha and IL-6 released into the medium were measured using an ELISA, Histamine weakly stimula ted IL-6 production by itself, However, together with UVB, it synergis tically enhanced IL-6 production and the amount of IL-6 mRNA as estima ted by reverse-transcription polymerase chain reaction (RT-PCR), Hista mine had a dose-dependent effect which was maximal at a concentration of 10(-5) M, and had no effect on the kinetics of IL-6 production. In contrast, histamine had no effect on IL-l alpha production by keratino cytes, The effect of histamine was completely blocked by pyrilamine, a n H1 receptor antagonist, and mimicked by the H1 receptor agonist, 2-m ethylhistamine, Whereas the H2 receptor antagonist, cimetidine, slight ly inhibited the effect of histamine and the effect of the H2 receptor agonist, 4-methylhistamine, was minute. These results show that hista mine augments UVB-induced IL-6 production by keratinocytes predominant ly via the H1 receptor at the level of transcription. This suggests a contributory role for histamine in the exacerbation of atopic dermatit is induced by sun exposure.