Effects of lidocaine on cytosolic pH regulation and stimulus-induced effector functions in alveolar macrophages

Local anesthetics influence a variety of stimulus-induced effector functions in leukocytes. The present study determined the effects of lidocaine on intracellular pH (pH(i)) regulation, superoxide production, and tumor necrosis factor-alpha (TNF-alpha) release in alveolar macrophages (m phi). Resident m phi were obtained by bronchoalveolar ravage of rabbits. The cells were subjected to an intracellular acid load, and subsequent pH(i) recovery was followed in the presence or absence of bafilomycin A(1), a specific inhibitor of V-type H+-translocating ATPase (V-ATPase) or amiloride, an inhibitor of Na+/H+ exchange. Lidocaine slowed pH(i) recovery in a dose-dependent manner. Pretreatment (1 h) with 2.5 mM lidocaine abolished Na+/H+ exchange and reduced the V-ATPase-mediated component of pH(i) recovery. Lidocaine also significantly depressed the superoxide production induced by phorbol ester. TNF-alpha release induced by endotoxin was not affected significantly by the local anesthetic. Macrophage viability (trypan blue exclusion) and cellular ATP concentration were unaffected. These results indicate that lidocaine inhibits pH(i) regulatory mechanisms in alveolar m phi. This disruption of pH(i) regulation could contribute to inhibitory actions of lidocaine on m phi effector functions.