Anti‐prolactin treatment alleviates lupus conditions by regulating the JAK2–STAT3 pathway

Abstract Objectives We previously revealed the role of prolactin (PRL) in antibody production and disease activity in patients with systemic lupus erythematosus. In this study, we sought to determine whether inhibition of PRL could improve lupus‐like disease in MRL/lpr mice. Methods The expression levels of PRL in various cell types of lupus patients were measured by flow cytometry. The effects of anti‐PRL on animal survival, renal histopathology, creatinine, proteinuria, anti‐dsDNA antibody, cytokine production, splenomegaly and lymphadenopathy were assessed. The effect of anti‐PRL on the Jak2‐Stat3 signalling pathway was detected by western blotting. Results Prolactin was upregulated in B cells, neutrophils, CD4+ T cells, and monocytes isolated from patients with lupus. Furthermore, inhibition of PRL by anti‐PRL treatment around the time of onset prolonged the survival of MRL/lpr mice, significantly reduced anti‐dsDNA antibody production, and alleviated symptoms of lupus nephritis, splenomegaly, and lymphadenopathy. In addition, anti‐PRL‐treated mice showed a decrease in the levels of pathogenic cytokines such as IL‐21 and IL‐6. Furthermore, mechanistically, anti‐PRL treatment significantly reduced the levels of p‐Jak2 and p‐Stat3 in MRL/lpr mice. Conclusions In summary, these data suggest that PRL inhibition alleviates lupus‐like disease in MRL/lpr mice by modulating the Jak2‐Stat3 signalling cascade. More importantly, our results imply the potential of PRL inhibitors and may provide a novel therapeutic approach for lupus.