IL-36γ与IL-38的表达失衡可能与寻常型银屑病的炎症程度相关

Imbalance of expression levels of IL-36γand IL-38 is possibly associated with the severity of inflammation in psoriasis vulgaris

目的探究细胞因子IL-36γ、IL-38在寻常型银屑病炎性反应中的作用。方法收集29例寻常型银屑病(PV)患者(包括轻中度14例,重度15例)及19例正常对照者血清及外周血单个核细胞(PBMC),使用ELISA法检测血清中IL-36γ及IL-38表达量,RT-qPCR检测PBMC中IL-36γ及IL-38 mRNA相对表达水平。收集12例使用IL-17A单抗治疗的银屑病患者血清及PBMC,检测IL-17A单抗治疗前及治疗4周后血清及PBMC中IL-36γ、IL-38表达水平。将IL-17A与HaCaT细胞共培养,在不同时间点收集细胞,通过RT-qPCR检测HaCaT细胞中IL-36γ、IL-38 mRNA表达水平变化。结果轻中度及重度PV患者血清IL-36γ表达水平均显著高于对照组(t值分别为12.27、16.45,均P<0.001),血清IL-38表达水平均显著低于对照组(t值分别为5.83、7.61,均P<0.001)。PV患者外周血PBMC中,IL-36γmRNA表达高于对照组,IL-38 mRNA表达低于对照组,差异均有统计学意义(均P<0.01)。使用IL-17A单克隆抗体治疗4周后:患者血清IL-36γ表达水平显著降低(t=3.24,P=0.004),IL-38表达水平显著升高(t=3.36,P=0.001);PBMC中IL-36γ及IL-38 mRNA表达水平具有相同趋势。IL-17A刺激致使HaCaT细胞IL-36γ表达水平出现增高,而IL-38表达水平降低。结论寻常型银屑病患者外周血中促炎因子IL-36γ表达明显增高,而抑炎因子IL-38表达明显受到抑制;IL-17A单克隆抗体治疗可在一定程度上逆转IL-36γ及IL-38表达水平,提示IL-36γ及IL-38可能在银屑病慢性炎症中发挥重要作用,且可能是作为协助评估银屑病患者病情严重程度以及银屑病生物制剂治疗疗效的重要血清学标记物。

Objective To investigate the roles of cytokines,IL-36γand IL-38,in the inflammatory response in psoriasis vulgaris.Methods Both serum and peripheral blood mononuclear cells(PBMC)were collected from 29 patients with psoriasis vulgaris(PV)and 19 healthy controls.PV group was divided into mild to moderate group(n=14)and severe group(n=15)according to psoriasis area and severity index(PASI).In addition,serum and PBMC were collected from 12 PV patients before and after the treatment with IL-17A monoclonal antibody(IL-17A mAb).Serum levels of IL-36γand IL-38 were measured using ELISA,and the relative expression levels of IL-36γand IL-38 mRNA in PBMC were determined using RT-quantitative real-time PCR(RT-qPCR).Moreover,human immortalized keratinocytes(HaCaT)cocultured with IL-17A were sampled at different time points to measure expression levels of IL-36γand IL-38 mRNA.Results Serum IL-36γlevels were significantly higher in patients with either mild to moderate or severe psoriasis than in healthy controls(t=12.27 and 16.45,respectively,P<0.001),but IL-38 levels were significantly lower in psoriatic patients than in healthy controls(t=5.83 and 7.61,respectively,P<0.001).In comparison to baseline levels,treatments of psoriasis with IL-17A mAb for 4 weeks markedly lowered serum levels of IL-36γ(t=3.24,P=0.004),while increasing IL-38 levels(t=3.36,P=0.001),along with similar changes in expression levels of IL-36γand IL-38 mRNA in PBMC of psoriatic patients.Moreover,IL-17A increased the expression levels of IL-36γmRNA,while decreasing expression levels of IL-38 in HaCaT cultures.Conclusions The expression levels of proinflammatory cytokine,IL-36γ,are significantly increased in peripheral blood of PV patients,while the expression levels of anti-inflammatory cytokine,IL-38,are significantly decreased.Treatments with IL-17A antibody reverse the expression levels of IL-36γand IL-38 to some extent,suggesting an essential role of IL-36γand IL-38 in chronic inflammation of psoriasis.IL-36γand IL-38 could serve as serological markers for the assessment of the efficacy of biologics for psoriasis.