Interleukin-12 exacerbates symptoms in an MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus

Li,Ling; Sun,Xiaojun; Wu,Sisi; Yuan,Xin; Liu,Bingxin; Zhou,Xueping

doi:10.3892/etm.2021.10059

Interleukin-12 exacerbates symptoms in an MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus

Authors:
- Ling Li
- Xiaojun Sun
- Sisi Wu
- Xin Yuan
- Bingxin Liu
- Xueping Zhou
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Affiliations: Department of Rheumatology, Taizhou Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou, Jiangsu 225300, P.R. China, Medical Intensive Care Unit, Ningbo Women and Children's Hospital, Ningbo, Zhejiang 315000, P.R. China, Department of Rheumatology, Jiangsu Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China, Institute of Acute Disorders of Traditional Chinese Internal Medicine, The First Clinical College of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
Published online on: April 15, 2021 https://doi.org/10.3892/etm.2021.10059
Article Number: 627
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Interleukin (IL)-12 modulates the generation and function of a variety of immune cells and serves an important role in the pathogenesis of autoimmune diseases. However, the precise role of IL-12 in the pathogenesis of systemic lupus erythematosus (SLE) remains to be elucidated. In the present study, the serum levels of IL-12 in patients with SLE were determined using an ELISA. The association between serum levels of IL-12 and clinical and laboratory indices, specifically, disease activity and complement 3, were analyzed. Recombinant IL-12 or an anti-IL-12 antibody was used to treat the MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus. The glomerulonephritis and inflammatory cell infiltration was examined to evaluate histological changes using hematoxylin and eosin and Periodic acid-Schiff staining. Serum creatinine and proteinuria were used to determine renal function. The levels of anti-double stranded DNA and anti-nuclear autoantibodies were assessed. The results demonstrated that serum levels of IL-12 were markedly increased in patients with SLE compared with controls and in lupus model mice in comparison with control mice. The serum levels of IL-12 increased with disease severity in patients with SLE. SLE-like symptoms were exacerbated in lupus model mice treated with exogenous IL-12. However, SLE-like symptoms were ameliorated in lupus model mice treated with an anti-IL-12 antibody. The present results demonstrated that IL-12 aggravated SLE and anti-IL12 antibodies ameliorated SLE. The present data suggest that blocking IL-12 may be a beneficial therapeutic strategy to halt the progression of lupus nephritis.

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