Inhibitory effect of azelastine, a potent antiallergic agent, on release of tumor necrosis factor-alpha from activated human peripheral blood mononuclear cells and U937 cells.
It is generally accepted that tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine which is involved in the regulation of inflammation as well as immunity. In the present study, we investigated whether azelastine, a potent antiallergic agent, affects release of TNF-alpha from peripheral blood mononuclear cells (PBMC) and U937 cell line in vitro. When human PBMC and U937 cells were stimulated by phytohemagglutinin (PHA) and 12-0-tetradecanoyl-phorbol-13-acetate (TPA), respectively, the cells released significant amounts of TNF-alpha as determined by TNF-alpha-specific enzyme immunoassay. TNF-alpha levels in the culture supernatant of PHA-stimulated human PBMC and TPA-activated U937 cells decreased in a dose-dependent manner when these cells were cultured in the presence of azelastine. This inhibitory effect of azelastine was obtained at concentrations where the drug produced no toxicity. Moreover, azelastine also inhibited release of TNF-alpha from U937 cells which were already activated by TPA. These results suggest that the inhibitory effect of azelastine on TNF-alpha release plays an important role in its antiallergic action in addition to inhibition and/or antagonism of histamine and leukotrienes, which has been previously reported.
Hamamoto
Y
Y
Department of Dermatology, Yamaguchi University School of Medicine, Japan.
Nagai
K
K
Muto
M
M
Asagami
C
C
D003864:Depression, Chemical; D003876:Dermatitis, Atopic / Q000097:blood / Q000473:pathology; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D010793:Phthalazines / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011565:Psoriasis / Q000097:blood / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D009363:Neoplasm Proteins; D010793:Phthalazines; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate; C020976:azelastine