Lidocaine inhibits the proliferative response and cytokine synthesis of peripheral blood mononuclear cells after allergen- and non-allergen-specific activation. In the present study, we investigated the role of apoptosis in the inhibitory effect of lidocaine on CD4
+ T-cells. CD4
+ T-cells from 8 patients with asthma and house dust mite allergy were cultured with lidocaine. Staining for Annexin V and propidium iodide was monitored by flow cytometry. The active forms of caspase-3 and caspase-9 were examined by flow cytometry and the expression of Bcl-2 was analyzed by immunoblotting. The inhibitory effects of lidocaine on CD4
+ T-cell proliferation and interleukin-5 and interferon γ production after stimulation with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore were also investigated. The extent of apoptosis in CD4
+ T-cells stimulated with PMA plus calcium ionophore was examined. Addition of lidocaine (1mM) to resting CD4
+ T-cells increased the percentage of Annexin V
+ PI
- Tcells in the culture (
P<0.01) ; expression of the active forms of caspase-3 and caspase-9 was increased (
P<0.05), while expression of Bcl-2 was decreased. The proliferative response (P<0.01) and the production of interleukin-5 and interferon-γ (
P<0.01) by CD4
+ T-cells after stimulation with PMA plus calcium ionophore were inhibited upon incubation with 1 mM lidocaine. Furthermore, the percentage of Annexin V
+ PI
- T-cells in activated CD4
+ T-cells treated with 1 mM lidocaine was also increased. Thus, lidocaine induces apoptosis in CD4
+ T-cells by activation of caspase-3 and caspase-9 and down-regulation of Bcl-2.
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