The Ca²⁺ Channel Blocker Verapamil Inhibits the In Vitro Activation and Function of T Lymphocytes: A 2022 Reappraisal

Abstract

Ca2+ channel blockers (CCBs) are commonly used to treat different cardiovascular conditions. These drugs disrupt the intracellular Ca2+ signaling network, inhibiting numerous cellular functions in different cells, including T lymphocytes. We explored the effect of the CCB verapamil on normal human peripheral blood T cell activation, proliferation, and cytokine production. Cells were activated by ligating CD3 or CD3/CD28 in the presence or absence of verapamil, and the expression of activation-induced cell surface molecules (CD25, CD40L, CD69, PD-1, and OX40), cell proliferation, and cytokine release were assessed by flow cytometry. Verapamil exerted a dose-dependent inhibitory effect on the expression of all the activation-induced cell surface molecules tested. In addition, verapamil diminished T cell proliferation induced in response to CD3/CD28 stimulation. Likewise, the production of Th1/Th17 and Th2 cytokines was also reduced by verapamil. Our data substantiate a potent in vitro suppressive effect of verapamil on T lymphocytes, a fact that might be relevant in patients receiving CCBs.

Keywords

• verapamil
• Ca²⁺ channel blockers
• immunosuppression
• T cell activation
• cytokine production