Xuyan Yang1, Qinjie Weng2, Lingzhen Hu3, Lijun Yang2, Xingxing Wang3, Xueping Xiang4, Bo Hong4, Xubo Gong5, Qingqing Wang6. 1. Department of Rheumatology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. hangzhouyxy@zju.edu.cn. 2. Institute of Pharmacology, College of Pharmaceutical Science, Zhejiang University, Hangzhou, China. 3. Department of Rheumatology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. 4. Department of Pathology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. 5. Laboratory of Bone Marrow, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. 6. Department of immunology, Institute of Basic Medical Sciences, College of Medicine, Zhejiang University, Hangzhou, China.
Abstract
OBJECTIVES: Interleukin-22 (IL-22) has been considered as an inflammatory cytokine. In the present study, we investigated the potential role of IL-22 in lupus nephritis (LN). METHODS: We examined the IL-22 levels of serum and kidney tissue from LN patients and MRL/lpr mice. An intraperitoneal injection of saline, isotype control antibody (IgG), prednisone (3mg/kg/mouse), or anti-IL-22 mAb (5μg/kg/mouse or 25μg/kg/mouse) was administered twice a week from 6 to 18 weeks of age. RESULTS: IL-22 levels in both serum and kidney were significantly higher in LN patients as compared with those in healthy controls. The serum and renal levels of IL-22 in MRL/lpr mice were significantly increased over time. After MRL/lpr mice were treated with anti-IL-22 monoclonal antibody (mAb) for 12 weeks, significantly less urine protein and lower serum levels of creatinine and urea nitrogen were found. In addition, less renal injury score and few number of inflammatory cells per glomerulus were observed in MRL/lpr mice treated with anti-IL-22 mAb as compared with control groups. CONCLUSIONS: Our results suggest that IL-22 as a pathogenic cytokine might be a potential target for treatment of lupus nephritis.
OBJECTIVES:Interleukin-22 (IL-22) has been considered as an inflammatory cytokine. In the present study, we investigated the potential role of IL-22 in lupus nephritis (LN). METHODS: We examined the IL-22 levels of serum and kidney tissue from LN patients and MRL/lpr mice. An intraperitoneal injection of saline, isotype control antibody (IgG), prednisone (3mg/kg/mouse), or anti-IL-22 mAb (5μg/kg/mouse or 25μg/kg/mouse) was administered twice a week from 6 to 18 weeks of age. RESULTS:IL-22 levels in both serum and kidney were significantly higher in LN patients as compared with those in healthy controls. The serum and renal levels of IL-22 in MRL/lpr mice were significantly increased over time. After MRL/lpr mice were treated with anti-IL-22 monoclonal antibody (mAb) for 12 weeks, significantly less urine protein and lower serum levels of creatinine and ureanitrogen were found. In addition, less renal injury score and few number of inflammatory cells per glomerulus were observed in MRL/lpr mice treated with anti-IL-22 mAb as compared with control groups. CONCLUSIONS: Our results suggest that IL-22 as a pathogenic cytokine might be a potential target for treatment of lupus nephritis.
Authors: Tilman Schmidt; Jonas Luebbe; Christoph Kilian; Jan-Hendrik Riedel; Sonja Hiekmann; Nariaki Asada; Pauline Ginsberg; Lennart Robben; Ning Song; Anna Kaffke; Anett Peters; Alina Borchers; Richard A Flavell; Nicola Gagliani; Penelope Pelzcar; Samuel Huber; Tobias B Huber; Jan-Eric Turner; Hans-Joachim Paust; Christian F Krebs; Ulf Panzer Journal: J Am Soc Nephrol Date: 2021-12 Impact factor: 10.121