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

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-Fas(lpr) 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.