The results showed that JS1287 small molecule alleviated epidermal thickness, epidermis congestion, edema and inflammatory cell infiltration, decreased release of inflammatory cytokines of IL-6, IL-12 and IL-17A, and further regulated the mRNA expression of ATF1 and protein expression of ERK1/2 in IMQ-induced skin lesions.
The levels of sICAM-1 in the skin tissue fluid and IL-6 and IL-17 in the blood of patients with vitiligo were positively correlated with the skin lesion area of patients (P<0.05).
The mRNA expression in blood and skin lesion for TNF, IFN-γ, IL-1β, IL-6, and IL-17A significantly reduced in patients with ENL after treatment, while mRNA expression for IL-10 and TGF-β was significantly increased both in blood and skin lesion after treatment.
In addition, psoriatic patients with MS showed a much less reduction of systemic biomarkers (interleukin-IL-17, TNF-α, IL-6) than patients without MS. Namely, they may need a longer course of treatment to achieve improved skin lesions.
In addition, significant association between the IL-6-174 G/C polymorphism and discoid skin lesions and antinuclear antibodies (ANAs) were found under the allelic contrast model and recessive model, respectively (discoid skin lesions: OR 2.271, 95% CI 1.053-4.895; ANAs: OR 2.244, 95% CI 1.141-4.416).
Neutralization of tumor necrosis factor-α and IL-6 (both downstream of IL-17A) reduced skin lesions, attenuated oxidative stress in heart and blood, and partially improved endothelial dysfunction in K14-IL-17A(ind/+) mice.
The review also dissects, based on information from mouse models of AD, the contributions of the innate and adaptive immune system to the pathogenesis of AD, including the effect of mechanical skin injury on the polarization of skin dendritic cells, mediated by keratinocyte-derived cytokines such as thymic stromal lymphopoietin (TSLP), IL-6, and IL-1, that results in a Th2-dominated immune response with a Th17 component in acute AD skin lesions and the progressive conversion to a Th1-dominated response in chronic AD skin lesions.
Genes coding for HHV-8-encoded viral interleukin-6, viral macrophage inflammatory protein I, viral G protein-coupled receptor, viral cyclin D and viral Bcl-2 were expressed to the same degree in both her skin lesion and PBMC.
Interactions between infiltrating T cells and keratinocytes via the secretion of the TH1 cytokines interleukin (IL) 2 and interferon gamma (INF-gamma), the keratinocyte growth factor transforming growth factor alpha (TGF-alpha) and the cytokines IL-6 and IL-8 are thought to be the predominant mechanisms inducing skin lesions in psoriatic patients.