Lidocaine in bronchoalveolar lavage fluid (BALF) is an inhibitor of eosinophil-active cytokines

Abstract

Eosinophils and eosinophil granule proteins may play an important role in the pathogenesis of asthma. BALF from 40 patients with symptomatic asthma were analysed for cytokine activity by the eosinophil survival assay. BALF from 15 patients showed increased survival activity. Survival activities in BALF from four of these patients were almost completely blocked by anti‐IL‐5 MoAb, and the remaining activities were blocked by anti‐granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), anti‐IL‐3 antibody, or both. Surprisingly, BALF samples from the other 25 patients decreased eosinophil viabilities below the levels of medium control. The inhibitory factor in these BALF was of low molecular weight, was heat‐stable, was largely overcome by excess exogenously added cytokines, and was positively correlated with the concentrations of lidocaine in the BALF. Lidocaine itself inhibited eosinophil survival at concentrations less than those present in the BALF. These findings indicate that lidocaine is an inhibitor of cytokines in the eosinophil survival assay, and they suggest the need for caution in analyses of BALF containing lidocaine or other local anaesthetics.

Local anaesthetic medication for the treatment of asthma

“…It was further demonstrated that lidocaine preferentially inhibited survival and activation of human eosinophils stimulated by cytokines, such as IL-5, IL-3 and GM-CSF, in a concentration dependent-manner (IC 50 ≅ 110 µM). Such an effect did not seem to be accounted for by the blockade of sodium channels and could not be explained by an action on either cytokine receptor expression or cytokine-induced protein tyrosine phosphorilation (Ohnishi et al 1996. Of note, these effects were not due to nonspecific cytotoxicity either, since (i) lidocaine inhibited eosinophil survival by causing apoptosis rather than necrosis; (ii) the mechanism of cell death was clearly time-dependent, requiring at least 24 h of exposure to lidocaine; and (iii) eosinophil survival and superoxide production induced by IgG, PAF or PMA were not modified by lidocaine, indicating that this local anaesthetic was not a general inhibitor of eosinophils ).…”

“…Interestingly, lidocaine also inhibits the function of non-excitable cells, particularly inflammatory cells, such as neutrophils, eosinophils, macrophages, mast cells and T H 2 cells, raising the promising possibility of alternative clinical applications on the control of chronic inflammatory diseases, including asthma (Hunt et al 1996, Ohnishi et al 1996, Hollmann & Durieux 2000, Tanaka et al 2002. Ohnishi et al (1996) incidentally discovered that concentrations of lidocaine as high as 10 mM could be detected in the broncoalveolar lavage fluids recovered from asthma patients subjected to bronchoscopy under lidocaine topical anesthesia, and that such an effluent was a strong inhibitor of eosinophil viability in vitro. It was further demonstrated that lidocaine preferentially inhibited survival and activation of human eosinophils stimulated by cytokines, such as IL-5, IL-3 and GM-CSF, in a concentration dependent-manner (IC 50 ≅ 110 µM).…”

Lidocaine Nebulization in the Treatment of Acute Severe Refractory Bronchial Asthma

“…Lidocaine is largely used in clinic as a shortacting local anaesthetic and antiarrhythmic agent [2]. Interestingly, lidocaine also inhibits the function of non-excitable cells, particularly inflammatory cells, such as neutrophils, eosinophils, macrophages, mast cells and TH2 cells, raising the promising possibility of alternative clinical applications on the control of chronic inflammatory diseases, including asthma [3][4][5][6][7].…”

Aerosolized Surfactants, Anti-Inflammatory Drugs, and Analgesics

“…78,79 Several uncontrolled studies suggest efficacy in mild-to-moderate asthma. A controlled blinded study by Hunt et al 80 in 50 adults with asthma administered 100 mg of lidocaine by aerosol versus saline 4 times/d showed improved FEV 1 , less nighttime awakening, decreased bronchodilator usage, and decreased blood eosinophil counts.…”

“…Nebulized lidocaine has already been mentioned as a potential aerosolized anti-inflammatory in asthma [78][79][80] and is a very effective topical anesthetic. Nebulized lidocaine has been purported to relieve the pain of nasogastric tube placement, 117 bronchoscopy, 118,119 and endotracheal intubation, 120 although not all studies show efficacy.…”