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Background: Histamine plays an important role in immediate and late immune responses. The histamine type 1 (H1) receptor is expressed on several immune cell populations, but its role in a murine model of asthma remains unclear. The present study evaluated the role of histamine H1 receptors in airway allergic inflammation by comparing the development of bronchial asthma in histamine H1 receptor gene knockout (H1RKO) and wild-type mice., Methods: H1RKO and wild-type mice were sensitized by intraperitoneal injection of ovalbumin (OVA) or saline, and then challenged with aerosolized OVA or saline. Ventilatory timing in response to inhaled methacholine was measured, and samples of blood, bronchoalveolar lavage, and lung tissues were taken 24 h after the last OVA challenge., Results: OVA-treatedwild-type mice showed significantly increased airway eosinophilic infiltration, and airway response to methacholine compared to OVA-treated H1RKO mice. The serum level of immunoglobulin E and levels of interleukin (IL)-4, IL-5, IL-13, and TGF-beta1 in bronchoalveolar lavage fluid were lower in OVA-treated H1RKO mice than in OVA-treated wild-type mice, but there was no significant difference in interferon-gamma expression. Overall, deletion of histamine H1 receptors reduced allergic responses in a murine model of bronchial asthma., Conclusion: Histamine plays an important role via H1 receptors in the development of T helper type 2 responses to enhance airway inflammation.

A house dust bronchial provocation test (BPT) was used to investigate the effect of allergen-induced airway inflammation and airway hyperresponsiveness (AHR) on the level of circulating intracellular adhesion molecule-1 (c-ICAM-1). The concentration of c-ICAM-1 was measured by the sandwich ELISA while the level of eosinophil cationic protein (ECP) in the sputum was determined by RIA. The parameter used for quantification of AHR was the minimum dose of methacholine (Mch) required to produce a fall in respiratory resistance and was expressed as log Dmin. Fourteen subjects with mild atopic asthma participated in this study. Ten patients (dual asthmatic response group; DAR group) developed a late asthmatic response (LAR) following an immediate asthmatic response (IAR). Four subjects (IAR alone group) exhibited only IAR following BPT. In both groups, the mean baseline concentration of c-ICAM-1 did not change 6 h after BPT (from 195.3+/-20.3 to 220.9+/-27.6 and from 215.5+/-23.5 to 231.3+/-30.5 ng/ml, respectively). However, BPT produced a significant increase in the mean concentration of c-ICAM-1 24 h later in the DAR group (257.3+/-41.14 ng/ml, p < 0.05), but not in the IAR alone group (225.5+/-18.1 ng/ml). BPT also increased ECP levels in the sputum from a baseline value 24 h after BPT in the DAR group (from 30.2+/-10.1 to 68.8+/-19.8 ng/ml; p<0.05), but not in the IAR alone group (from 28.1+/-8.3 to 43.3+/-23.7 ng/ml). There was a significant (p<0.05) correlation between c-ICAM-1-concentrations and sputum ECP levels 24 h after BPT in each group. Furthermore an inverse and significant (p<0.05) correlation was found between c-ICAM-1 concentrations and percent changes in log Dmin 24 h after BPT in each group. Our results suggest that increased concentrations of c-ICAM-1 after BPT may reflect the upregulated expression of airway ICAM-1 during allergen-induced airway inflammation. We propose that c-ICAM-1 is a useful marker for allergic inflammation, particularly that of eosinophilic infiltration into the airway, an essential feature of asthma.