Background: Diffuse alveolar hemorrhage (DAH) represents one of the most severe complications of systemic lupus erythematosus (SLE), its mortality rate reaches 65%–90%, indicating extremely poor prognosis. Current clinical treatment primarily involves high-dose glucocorticoid pulse therapy combined with immunosuppressants, supplemented by respiratory support and plasma exchange. However, these strategies are of limited efficacy and are often associated with adverse effects such as infection, hypertension, and adrenal suppression.

Objectives: This study aimed to evaluate the therapeutic efficacy and mechanism of interleukin-2 (IL-2) in a pristane-induced murine model of lupus-associated DAH.

Methods: C57BL/6J mice received intraperitoneal pristane injection to induce lupus-like DAH. IL-2 was administered at varying doses. Disease severity, histopathological alterations, inflammatory infiltration, cytokine profiles, T cell subsets, and apoptosis were assessed using hematoxylin and eosin staining, immunohistochemistry, flow cytometry, ELISA, and TUNEL assays. Transcriptomic sequencing of lung tissue was performed to identify IL-2 treatment related molecular pathways.

Results: IL-2 treatment reduced the incidence and severity of DAH in a dose-dependent manner, with the 100,000 U dose achieving the best therapeutic effect. Treated mice exhibited improved weight maintenance, reduced lung weight, enhanced survival, ameliorated histopathological damages in lungs with decreased pulmonary infiltration of F4/80+ macrophages and lowered levels of TNF-α, IL-6, IL-10, MIP-1, and SDF-1 in bronchoalveolar lavage fluids and peripheral blood. IL-2 treatment also increased CD4+ regulatory T cells, reduced effector T cells, improved the Treg/Tcon ratio, and improved Th1/Th2 imbalance. Pulmonary IgM deposition and apoptotic cell accumulation were also reduced. Transcriptomic analysis revealed that the IL-2 therapy corrected widespread gene expression abnormalities, suppressing pathways associated with inflammation, chemotaxis, adhesion, and innate immunity, while downregulating IL-6, TNF, IL-1, and Toll-like receptor signaling.

Conclusions: IL-2 treatment improved murine lupus-associated DAH by restoring T cell homeostasis, suppressing inflammatory cascades, and regulating apoptosis and transcriptomic networks. These findings underscore the potential of IL-2 as a therapeutic candidate for SLE-related DAH and provide novel mechanistic insights for translation.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.