靶向免疫代谢在治疗自身免疫和炎症性疾病方面显示出了潜力。脓疱性汗腺炎（HS）是一种慢性的炎症性皮肤疾病，涉及到富含分泌腺的皮肤上的痛苦性损伤。对于HS的治疗选择有限且常常无效，因此迫切需要改进的治疗方法。到目前为止，HS的代谢失调尚未进行研究。由于HS高度炎症性，我们假设能量代谢在这些患者中发生了失调。二甲双胍是一种抗糖尿病药物，已经被证明在癌症和关节炎中具有抗炎作用，并且已被HS患者使用二甲双胍的临床症状得到改善。为了评估二甲双胍在体内的作用，我们比较了使用二甲双胍和不使用二甲双胍的HS患者的外周血单个核细胞（PBMC）的免疫和代谢特征。为了检查二甲双胍治疗在体外的作用，我们使用来自不使用二甲双胍的HS患者的皮肤活检样本进行皮肤培植模型，然后与二甲双胍一起培养过夜。我们使用ELISA，多重细胞因子测定和定量RT-PCR来测量炎症标志物，使用海马测量技术和定量RT-PCR来评估葡萄糖代谢。我们显示出HS患者的PBMC中的代谢通路与健康个体相比发生了失调。在使用二甲双胍的患者中，这些代谢通路得到了恢复，并且长期使用二甲双胍治疗后，他们的PBMC的炎症标志物减少。在皮肤培植模型中，我们发现与二甲双胍的过夜培养减少了HS患者的损伤和道的炎症细胞因子和趋化因子以及糖酵解基因。使用体外实验，我们发现二甲双胍可能通过NLRP3炎症小体和AMPK-mTOR通路诱导这些变化，该通路与糖酵解和蛋白质合成相关。我们的研究揭示了二甲双胍在HS中的作用机制。二甲双胍的抗炎作用支持其作为HS的治疗药物的使用，而其对免疫代谢的影响表明靶向代谢是治疗炎症性疾病的一个有前途的选择，包括HS。 ©2023年作者发表。由牛津大学出版社代表英国皮肤科医师协会出版。

Targeting immunometabolism has shown promise in treating autoimmune and inflammatory conditions. Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease involving painful lesions in apocrine gland-bearing skin. Therapeutic options for HS are limited and often ineffective, thus there is a pressing need for improved treatments. To date, metabolic dysregulation has not been investigated in HS. Since HS is highly inflammatory, we hypothesise that energy metabolism is dysregulated in these patients. Metformin, the anti-diabetic drug, which is known to impact cellular metabolic and signalling pathways, has been shown to have anti-inflammatory effects in cancer and arthritis. While metformin is not licenced for use in HS, HS patients taking metformin show improved clinical symptoms.To assess the effect of metformin in vivo, we compared the immune and metabolic profiles of peripheral blood mononuclear cells (PBMC) of HS patients taking metformin versus those not taking metformin. To examine the effect of metformin treatment ex vivo, we employed a skin explant model on skin biopsies from HS patients not taking metformin, which we cultured with metformin overnight. We used ELISA, multiplex cytokine assays and quantitative RT-PCR to measure inflammatory markers, and Seahorse flux technology and quantitative RT-PCR to assess glucose metabolism.We showed that metabolic pathways are dysregulated in the PBMC of HS patients compared to healthy individuals. In the metformin-treated patients, these metabolic pathways were restored, and their PBMC had reduced inflammatory markers following long-term metformin treatment. In the skin explant model, we found that overnight culture with metformin reduced inflammatory cytokines and chemokines and glycolytic genes in lesions and tracts of HS patients. Using in vitro assays, we found that metformin may be inducing these changes via the NLRP3 inflammasome and the AMPK-mTOR pathway, which is linked to glycolysis and protein synthesis.Our study provides insight into the mechanisms of action of metformin in HS. The anti-inflammatory effects of metformin support its use as a therapeutic agent in HS, while its effects on immunometabolism suggest that targeting metabolism is a promising therapeutic option in inflammatory diseases, including HS.© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.