Ethanol enhances the IFN-gamma, TGF-alpha and IL-6 secretion in psoriatic co-cultures.

Evidence suggests an association between alcohol consumption and psoriasis. This relationship is still undefined, although long-term alcohol intake influences the immune system. Interactions between T cells and keratinocytes are important for the pathogenesis of psoriasis, by secretion of pro-inflammatory cytokines and growth factors in psoriatic skin. IL-2, IL-6, IL-8, IFN-gamma and TGF-alpha are hallmark cytokines in a psoriatic cytokine network. We investigated whether ethanol influences the secretion of these cytokines using a co-culture model with keratinocytes from psoriatic patients (n = 9) or from healthy controls (n = 9), with HUT 78 lymphocytes, and determined the cytokine levels with or without ethanol treatment in the culture supernatants. TGF-alpha and IFN-gamma levels were elevated in the ethanol-treated psoriatic co-cultures, to 150% and 175% respectively, but neither in co-cultures with keratinocytes derived from healthy control individuals nor in monocultures. Treatment with ethanol elevated slightly the IL-6 levels in the monocultures from psoriatic and control keratinocytes to 125% but not in HUT 78 monocultures. In the psoriatic co-cultures, IL-6 levels were elevated in the culture supernatants to almost 160%, but they were not influenced by ethanol in co-cultures with control keratinocytes. The cytokine levels of IL-8 or IL-2 were not significantly influenced in the psoriatic mono- and co-cultures or in HUT 78 cultures. If ethanol influences the cytokine secretion of psoriatic keratinocytes and HUT 78 lymphocytes in co-culture conditions, these data suggest that ethanol could also influence the psoriatic cytokine network in vivo, which may explain the explain the aggravation of this disease in alcohol-consuming psoriatic patients.

Lithium and psoriasis: cytokine modulation of cultured lymphocytes and psoriatic keratinocytes by lithium.

The predominant cutaneous side effect of lithium is the exacerbation or aggravation of psoriasis, but the pathogenesis is still unclear. The hyperproliferation of keratinocytes and a dense lesional infiltrate of mononuclear cells are the hallmarks of psoriatic skin lesions. Interactions between keratinocytes and T cells are thought to be one reason for an increased secretion of proinflammatory cytokines and growth factors. To investigate whether lithium influences cytokines of the "psoriatic cytokine network', we established a coculture model with keratinocytes from psoriatic patients and from healthy controls cultured with HUT 78 lymphocytes and measured the cytokine levels of Il-2, Il-6, Il-8, IFN gamma and TGF alpha in the culture supernatants after treatment with lithium. Il-6 levels were slightly elevated in the supernatants obtained from psoriatic and control keratinocyte cultures after lithium treatment, but IFN gamma and Il-2 levels were elevated only in the lithium-treated cocultures with psoriatic keratinocytes. In contrast, these two cytokines were not affected by lithium in HUT 78 monocultures or in cocultures with normal epidermal cells. We also found slightly elevated TGF alpha levels in lithium-treated psoriatic cocultures but not in control cultures. We therefore demonstrated that lithium influences the cell communication of psoriatic keratinocytes with HUT 78 lymphocytes by triggering the secretion of TGF alpha, Il-2 and, massively, IFN gamma. It seems possible that lithium also influences similar parts of the psoriatic cytokine network in vivo.