Aim: Superfluous reactive nitrogen and oxygen species generation is implicated in the damage of tissues at sites of inflammation where activated neutrophils and macrophages are involved. This study was conducted to investigate whether the beneficial effects of carvedilol involve modulation of respiratory burst, degranulation-myeloperoxidase release and inducible nitric oxide synthase (iNOS) expression. Methods: Spectrophotometry and chemiluminescence were used to evaluate the effect of carvedilol on opsonized zymosan (0.5 mg/ml)- or N-formyl-methionyl-leucyl-phenyl-alanine (fMLP, 0.1 µmol/l)-stimulated superoxide generation and myeloperoxidase release in human neutrophils. Western blot analysis was used for iNOS expression and Griess reagent for nitric oxide production in RAW 264.7 macrophages (lipopolysaccharide (0.1 µg/ml) stimulated). Results: Carvedilol (10 and 100 µmol/l) significantly decreased opsonized zymosan- and fMPL-stimulated superoxide generation and myeloperoxidase release. Carvedilol (100 µmol/l) enhanced the effect of wortmannin (50 nmol/l), a specific inhibitor of 1-phosphatidylinositol 3-kinase and decreased iNOS expression and nitric oxide production. Conclusion: Carvedilol appears to have a non-specific effect on membranes and to interfere with the phospholipase D signaling pathway, with subsequent inhibition of reactive oxygen species generation and myeloperoxidase release, without affecting iNOS expression.

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Chloroquine liberated a relatively low amount of histamine from isolated rat mast cells. In a dose-dependent way, this drug inhibited histamine liberation from mast cells stimulated with compound 48/80, A23187, concanavalin A plus phosphatidylserine (Con A + PS) and abolished histamine liberation induced by exaprolol. The degranulation was decreased in cells stimulated with 48/80, Con A + PS and exaprolol. Chloroquine significantly inhibited the formation of thromboxane B2 in mast cells stimulated with 48/80, Con A + PS and A23187. We assume that chloroquine interferes with mast cells at a plasmic membrane site as well as intracellularly.

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Activated neutrophils represent the main source of myeloperoxidase (MPO), superoxide (SO) and subsequently derived oxygen metabolites. They have important microbicidal activities, however in inflammatory conditions they may secondarily attack surrounding tissues. Overproduction of reactive oxygen species, prolonged or excessive liberation of MPO and other effective yet also toxic substances from neutrophils may participate in disturbed apoptosis, intensify the inflammatory processes and result in serious human diseases. The inhibitory effect of quercetin on PMA stimulated SO generation in isolated human neutrophils was found to be dose-dependent, without affecting the activity of intact isolated neutrophils. At comparable conditions, quercetin was more potent in inhibiting MPO release than SO generation. Our results indicate that quercetin could support resolution of inflammation through decreased activity of neutrophils, i.e. respiratory burst and degranulation.