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Interactions of Tofacitinib and Dexamethasone on Lymphocyte Proliferation
Ruihong Yu1, Xiaonan Li2, Debra C DuBois2,3
1Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
Purposes:
Lymphocyte proliferation is a major factor determining the magnitude of the immune response. Both dexamethasone (DEX) and tofacitinib (TOF) exert marked immunosuppressive effects and are mainstay drugs in the treatment of rheumatoid arthritis (RA). This study was aimed to explore the single and combined anti-proliferative action of DEX and TOF on lymphocytes and their sex differences.
Methods:
The single-drug effects and dual-drug interactions of TOF and DEX were assessed on the in vitro concanavalin A-stimulated proliferation of lymphocytes isolated from male and female rat and human peripheral blood.
Results:
DEX was more potent than TOF across species and sex. DEX showed greater inhibition on rat lymphocytes compared to those from humans, which was reflected in both Imax and IC50. The antiproliferative action of TOF was comparable in rats and humans with exception of a higher IC50 in male rats. Both sex- and species-related differences were detected in DEX/TOF interactions with synergistic effects in male lymphocytes, and additive and antagonistic effect for females in humans and rats.
Conclusion:
TOF has a promising steroid-sparing potential with the beneficial effects of the combination therapy more likely in males than females.
