leukotriene-d4 and Bronchitis

It has been demonstrated that both cysteinyl leukotrienes (cysLTs) and cytokines are involved in the pathophysiology of bronchial asthma. Nonetheless, the exact mechanism involved in the interaction between these 2 molecules has yet to be determined.. The aim of the present study was to determine the effects of cysLTs on allergic airway inflammation and allergen-specific cytokine production in a murine model of asthma.. Four groups of BALB/c mice (control mice, Dermatophagoides farinae allergen-sensitized mice, pranlukast cysLT receptor antagonist-treated allergen-sensitized mice, and dexamethasone-treated allergen-sensitized mice) were examined.. Allergen-sensitized mice exhibited increased airway responsiveness and inflammation. Pranlukast-treated mice showed significant attenuation of these changes concomitant with reduction of T(H)2 cytokine and IFN-gamma production by isolated lung mononuclear cells (MNCs). A much stronger inhibition of all cytokines was noted in dexamethasone-treated mice. Pranlukast also significantly inhibited production of RANTES and activation of nuclear factor kappa B (NF-kappa B) in the isolated lung MNCs. Leukotriene D(4) stimulated isolated lung MNCs to produce RANTES but not any other cytokines and also activated NF-kappa B in these cells.. Our results suggest that cysLTs activate NF-kappa B and induce RANTES production from isolated lung MNCs, which in turn might cause migration of eosinophils and activated T lymphocytes into the airway.

Topics: Animals; Antigens, Dermatophagoides; Asthma; Bronchial Hyperreactivity; Bronchitis; Chemokine CCL5; Chromones; Cysteine; Cytokines; Female; Inflammation Mediators; Leukotriene Antagonists; Leukotriene D4; Leukotrienes; Lung; Mice; Mice, Inbred BALB C; Monocytes; NF-kappa B; Transcription Factor RelA

Brown-Norway (BN) rats develop airway hyper-responsiveness and lung eosinophilia 18-24 h after ovalbumin (OA) challenge. We hypothesized therefore that allergen-induced airway inflammation would further enhance airway responses to a subsequent antigen challenge. Animals were sensitized to both OA and bovine serum albumin (BSA) and, 14 days later, challenged by aerosols with both antigens 24 h apart. Measurements of pulmonary resistance (RL) were made for 8 h after the second antigen challenge and bronchoalveolar lavage (BAL) was performed. Animals were divided into three groups and received two challenges as follows: saline-BSA (n=9), OA-saline (n=8) and OA-BSA (n=10). Sensitization was confirmed by measurements of specific OA-IgE and BSA-IgE. Early responses [determined as the highest value of RL within the first 30 min after the challenge] were absent in all study groups. The late responses [determined from the area under the RL versus time curve from 120 to 480 min after the challenge] were significantly greater in animals challenged with BSA (15.16+/-3.86) compared to saline (3.76+/-4.09; P<0.05). However previous exposure to OA did not further increase the late response in animals subsequently challenged with BSA (20.11+/-3.67) despite enhanced airway responsiveness to LTD4 at this time point. BAL eosinophils and lymphocytes were significantly increased following BSA challenge in previously OA-challenged animals, compared to numbers retrieved from animals previously exposed to saline (P<0.05). These data indicate that previous exposure to OA did not further increase the LR to a second antigen challenge despite substantial increases in airway inflammatory cells and airway hyper-responsiveness to LTD4.

Topics: Animals; Antigens; Bronchi; Bronchial Provocation Tests; Bronchitis; Bronchoalveolar Lavage Fluid; Immunoglobulin E; Leukotriene D4; Male; Ovalbumin; Rats; Serum Albumin