In addition, the cytokine imbalance of psoriasis is clearly illustrated by therapeutic response https://www.selleckchem.com/products/pifithrin-alpha.html to IL-4 . Patients treated with recombinant human IL-4 showed a reduction of clinical scores, lesional Th1 cells, and the IFN-γ/IL-4 ratio, whereas the number of circulating Th2 cells was increased . This study clearly highlights the adjustment
of the disease-specific cytokine imbalance as an important therapeutic tool. In contrast to psoriasis, the skin of atopic eczema patients is frequently colonized by staphylococci, in particular S. aureus (reviewed in ). This phenomenon is due to a tissue-restricted immune deficiency that relates to the Th2-dominated cytokine microenvironment typically observed in atopic eczema. In vitro, both, IL-4 and IL-13, have been shown to inhibit Th1-  and Th17-mediated  induction of antimicrobial TSA HDAC supplier peptides in epithelial cells via STAT6 and SOCS molecules . The clinical relevance of these two opposing T-cell cytokine signatures has been shown in vivo in a rare population of patients suffering from both psoriasis and atopic eczema in parallel . In such patients, only eczema
lesions, but not psoriasis plaques, were colonized by S. aureus . Beyond insufficient epithelial immunity, a second hallmark of atopic eczema is an impaired epidermal barrier with consequent transepidermal water loss and dryness of the skin (reviewed
in ). While mutations in genes of the epidermal differentiation complex, such as filaggrin, are strongly associated with atopic eczema, a Th2-dominated microenvironment also damages the epidermal barrier by downregulating filaggrin and other genes of the epidermal differentiation complex [60-62]. Thus, Th2 cytokines antagonize Th1 and Th17 immunity in the skin and largely explain the phenotype of atopic eczema . A third cutaneous model disease is ACD. Here, small and harmless molecules (haptens) such as nickel elicit an acute eczematous immune response characterized by T-cell cytotoxicity and keratinocyte apoptosis [63, 64]. The clinical phenotype check details of ACD is largely explained by the cytokine content of the local microenvironment. Depending on the eliciting hapten, a mixed T-cell infiltrate is observed with dominating Th1 cytokines. In such a microenvironment, IL-17 functions as an amplifier of nonspecific T-cell apoptosis mediated by IFN-γ  and enhances the cytotoxic immune response typical for ACD. In summary, the function of T-cell cytokines strongly varies depending on the cytokine content of the local microenvironment. Therefore, the function of Th-cell subsets has to be interpreted within the context of the microenvironment and disease setting.