The effect of azelastine on the early allergic response

Abstract

To study the effect of azelastine on the immediate reaction to nasal allergen challenge, we performed a double blind, placebo-controlled cross-over clinical trial. Thirteen subjects with seasonal allergic rhinitis underwent nasal challenge with antigen 4 hr after a single oral 2 mg dose of azelastine. The response was monitored by counting the number of sneezes and by measuring the levels of histamine, prostaglandin D2, immunoreactive sulphidopeptide leukotrienes, kinis and TAME-esterase activity in recovered nasal lavages. After a single dose of azelastine, there was a significant reduction in sneezing (10 vs 2, P = 0.01) and in the median levels of recovered TAME-esterase activity (63.1 vs 17.5 c.p.m. x 10(-3), P = 0.01), immunoreactive sulphidopeptide leukotrienes (7.5 vs 2.1 ng/ml, P = 0.03) and kinins (1370 vs 251 pg/ml, P = 0.03), with no significant reduction in the median levels of histamine (3.7 vs 1.2 ng/ml, P = 0.2) and prostaglandin D2 (70 vs 70 pg/ml, P = 0.2) compared to placebo (numbers represent total increase over diluent challenge). These results suggest that azelastine does not inhibit mast cell activation but affects the consequences of released histamine, namely sneezing, increased vascular permeability and the generation of kinins. The results further suggest that other cells, in addition to mast cells, might be responsible for the generation of leukotrienes during the early allergic response, and that azelastine reduces their ability to generate this mediator or that inhibition of leukotriene release from mast cells occurs at lower drug concentrations.

Azelastine Inhibits Secretion of IL-6, TNF-α and IL-8 as well as NF-κB Activation and Intracellular Calcium Ion Levels in Normal Human Mast Cells

“…The present results indicate that azelastine, a histamine-1 receptor antagonist, can inhibit the secretion of proinflammatory cytokines IL-6, IL-8 and TNF-α more efficiently than histamine or tryptase. Inhibitory effects of azelastine had been reported in asthma and nasal allergy [8], as well as on the release of TNF-α from rat basophilic leukemia cells [9]and human leukemic mast cells [12]. Histamine-1 receptor antagonists had previously been shown to inhibit mast cell granule-stored mediators [7], as well as cytokine release from human leukemic mast cells (HMC-1) [25].…”

“…Certain histamine-1 receptor antagonists have variable antiallergic effects [7]. Azelastine has been shown to inhibit the early allergic response [8]and tumor necrosis factor-α (TNF-α) secretion from basophil leukemia cells [9]. However, the effect of azelastine on the release of proinflammatory cytokines from human cord blood-derived cultured mast cells (hCBMC) has not been investigated.…”

Azelastine HCl: A Review of the Old and New Formulations

“…25 Other studies have shown that treatment with azelastine HCl also decreased LTB4, LTC4 and LTD4 levels. 26,27 Treatment with azelastine HCl has been demonstrated to cause a significant decrease (P  0.05) in Substance P and kinin levels. 26,27 Studies investigating the effect of azelastine HCl on mast cells have demonstrated decreased release of inflammatory cytokines and inhibition of tumor necrosis factor alpha.…”

“…26,27 Treatment with azelastine HCl has been demonstrated to cause a significant decrease (P  0.05) in Substance P and kinin levels. 26,27 Studies investigating the effect of azelastine HCl on mast cells have demonstrated decreased release of inflammatory cytokines and inhibition of tumor necrosis factor alpha. [27][28][29] In a double-blind study in AR patients, a significant decrease in neutrophils and eosinophils along with decreased expression of intercellular adhesion molecules was observed.…”

“…26,27 Studies investigating the effect of azelastine HCl on mast cells have demonstrated decreased release of inflammatory cytokines and inhibition of tumor necrosis factor alpha. [27][28][29] In a double-blind study in AR patients, a significant decrease in neutrophils and eosinophils along with decreased expression of intercellular adhesion molecules was observed. 22 In order to assess the effect of azelastine HCl on airway inflammation, exhaled nitric oxide (eNO) levels were measured before and after treatment.…”