Ethanol enhances the IFN-γ, TGF-α and IL-6 secretion in psoriatic co-cultures

Abstract

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.

The antipsoriatic agent dimethylfumarate immunomodulates T-cell cytokine secretion and inhibits cytokines of the psoriatic cytokine network

“…As expected, 1 –3 , 7 , 8 we measured higher cytokine levels of IL‐6 and TGF‐α in the psoriatic mono‐ and cocultures ( P < 0.05) than in the cultures with control keratinocytes ( Table 1). The cocultivation of HUT 78 T cells with keratinocytes did not alter the cytokine concentrations compared with monocultures, with the exception that the IFN‐γ secretion of HUT 78 T cells was raised above 50% under coculture conditions.…”

“…Keratinocyte cultures were performed with standard methods in RPMI‐1640 medium supplemented with 10% heat‐inactivated fetal calf serum (FCS) in view of the coculture conditions. In passages 4–5, keratinocytes were cocultivated with HUT 78 T cells as described previously 7 ,. 8 HUT 78 T cells (ATCC, Rockville, MD, U.S.A.) are a continuously activated T‐cell lymphoma cell line growing in RPMI‐1640 supplemented with 10% FCS 9 .…”

“…Because almost nothing was known about the antipsoriatic mechanisms of FAEs at the cellular level, we investigated the effect of FAEs on the psoriatic cytokine network. Therefore, keratinocytes were mono‐ or cocultured in a recently described coculture model 7 , 8 with/without FAEs and cytokine mRNA induction in the cells; cytokine levels in the culture supernatants were also determined.…”

Dietary Behaviors in Psoriasis: Patient-Reported Outcomes from a U.S. National Survey

“…Excessive alcohol intake has been associated with the development of psoriasis and is correlated with psoriasis severity [44, 45]. Proposed mechanisms for the interaction of alcohol in psoriasis include enhancement of mitogen-driven lymphocyte proliferation and upregulation of pro-inflammatory cytokines [46, 47]. …”

Triggermechanismen der Psoriasis

“…Vincenti berichtete von 3 Patienten, deren chronische Psoriasis sich bereits nach 6-wöchi-ger Abstinenz mit oder ohne psoriatische Therapie fast vollständig zurückbildete. Wie bei den anderen medikamentösen Provokatoren exazerbierte die Psoriasis bei neuerlicher Alkoholeinnahme [17].…”