Guenova Emmanuella, Teske Anna, Fehrenbacher Birgit, Hoerber Sebastian, Adamczyk Annette, Schaller Martin, Hoetzenecker Wolfram, Biedermann Tilo
Department of Dermatology, Eberhard Karls University Tübingen, Liebermeisterstrasse 25, 72076 Tübingen, Germany.
Arch Dermatol. 2011 Oct;147(10):1203-5. doi: 10.1001/archdermatol.2011.168. Epub 2011 Jun 16.
Interleukin (IL)-23 is involved in the pathogenesis of the chronic inflammatory Crohn disease. Pyoderma gangrenosum (PG) is often associated with and can even be the first manifestation of this disease and has abundant neutrophilic infiltration. Because IL-23 plays a critical role in driving inflammation associated with IL-17 production and especially neutrophil recruitment, we suspect that PG might be driven by a pathogenetic mechanism similar to that of inflammatory bowel diseases or psoriasis.
Tissue sample analysis showed highly elevated expression of IL-23 on both transcriptional and protein level in a recalcitrant PG lesion. On the basis on these data, a treatment targeting the p40 subunit of the heterodimeric IL-23 with the monoclonal antibody ustekinumab was started. Therapy with ustekinumab resulted in a significant decrease of IL-23 expression in PG and healing after 14 weeks of treatment. No relapse occurred in a 6-month follow-up period.
Our data provide evidence of an IL-23-dominated inflammatory infiltrate in PG. This might specify a new concept for PG pathophysiology and suggests a possibility for using ustekinumab as a therapeutic agent in this disease.
白细胞介素（IL）-23参与慢性炎症性克罗恩病的发病机制。坏疽性脓皮病（PG）常与该病相关，甚至可能是其首发表现，且有大量中性粒细胞浸润。由于IL-23在驱动与IL-17产生相关的炎症尤其是中性粒细胞募集中起关键作用，我们怀疑PG可能由与炎症性肠病或银屑病类似的发病机制所驱动。
组织样本分析显示，在一个顽固性PG皮损中，IL-23在转录水平和蛋白水平均有高度上调表达。基于这些数据，开始使用单克隆抗体优特克单抗针对异二聚体IL-23的p40亚基进行治疗。优特克单抗治疗导致PG中IL-23表达显著降低，并在治疗14周后愈合。在6个月的随访期内未出现复发。
我们的数据提供了PG中以IL-23为主导的炎性浸润的证据。这可能为PG的病理生理学指明一个新概念，并提示将优特克单抗用作该病治疗药物的可能性。
