Rucaparib enhances IL-2 production in EL-4 T cells and splenocytes.

BACKGROUND

Interleukin-2 (IL-2) is a pivotal cytokine that regulates T cell activation, proliferation, and survival, and plays a central role in shaping adaptive immune responses. Modulation of IL-2 production has therefore been considered an important strategy for enhancing immune function in various disease settings, including cancer and immunodeficiency. Recent advances in drug repurposing have highlighted the potential of FDA-approved compounds as novel immunomodulatory agents with well-characterized safety profiles. In this study, we screened an FDA-approved drug library and identified the PARP inhibitor rucaparib as a compound that enhances IL-2 production in EL-4 T cells and splenocytes.

RESULTS

Rucaparib significantly increased IL-2 production in murine EL-4 T cells under both unstimulated conditions and following activation with Phorbol 12-myristate 13-acetate (PMA) and ionomycin (Io), without affecting cell viability. In primary mouse splenocytes, rucaparib enhanced IL-2 production under concanavalin A (ConA) stimulation and increased tumor necrosis factor-α (TNF-α) production in response to lipopolysaccharide (LPS), with no detectable cytotoxicity. In vivo, BALB/c mice administered rucaparib (5 or 10 mg/kg) for one week showed no cytotoxic effects in isolated splenocytes under either basal or mitogen-stimulated conditions. Mechanistically, rucaparib enhanced IL-2 and NF-κB promoter activities in PMA/Io stimulated EL-4 T cells, indicating transcriptional activation of T cell signaling pathways.

CONCLUSION

Rucaparib enhances cytokine production and transcriptional activation in immune cells without inducing cytotoxicity, suggesting its potential as a modulator of T cell-mediated immune responses.