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Lidocaine inhibits the proliferative response and cytokine synthesis of peripheral blood mononuclear cells after allergenand 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 y 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 (1 mM) to resting CD4+ T -cells increased the percentage of Annexin V+ PITcells 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<o.ol) and the production of interleukin-5 and interferon-y (P<o.ol) 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+ PIT -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.

Lidocaine Induces Apoptosis in Peripheral CD4+ T-cells of Patients with Bronchial Asthma