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Background: The anti-inflammatory potential of antihistamines has significant clinical utility. Long-term pharmacotherapy of so-called 'safe' antihistamines may be hampered by side effects in the central nervous system. In the present study, the new potential antihistamine SUN-1334H was compared with different antihistamines for anti-inflammatory effects, sedation potential and interaction with alcohol., Method: Nasal and skin allergy were induced in guinea pig and mice by ovalbumin sensitization and challenge. Neurogenic nasal inflammation was induced by capsaicin. Sedation potential and interaction with alcohol were assessed by i.v. and intracerebroventricular pentobarbital-induced sedation and alcohol-induced ataxia models., Results: Ovalbumin sensitization and challenge caused rhinitis pathology including inflammatory cell infiltration, IL-4, and protein leakage in the nasal lavage fluid (NLF) and presence of inflammatory cells in nasal epithelium. A 5-day treatment of antihistamines reduced these markers of inflammation. SUN-1334H, cetirizine and hydroxyzine caused comparable inhibition of NLF leukocytes, IL-4 and total protein concentrations. Fexofenadine and desloratadine showed moderate inhibition of NLF leukocytes and had no significant effect on IL-4 concentration. While fexofenadine had no effect on total protein concentration, the effect of desloratadine was comparable with the other antihistamines. In neurogenic nasal inflammation induced by capsaicin, SUN-1334H and fexofenadine caused better inhibition at lower and middle dose levels than the other antihistamines. In skin allergy models, SUN-1334H showed potent reduction of passive and active cutaneous anaphylactic reactions. In central nervous system side effects models, SUN-1334H, desloratadine and fexofenadine were devoid of any significant effects., Conclusions: The results are suggestive of a high anti-inflammatory to sedation index of SUN-1334H among leading antihistamines.

Background: The literature on abnormality of vasomotor responses of the nasal mucosa to cold stimulation of the skin in idiopathic rhinitis is conflicting. The objective of this study was to elucidate pathophysiological features of the nasal mucosa in idiopathic rhinitis compared to allergic rhinitis., Methods: The following were studied in patients with idiopathic rhinitis and allergic rhinitis and in normal controls: (1) threshold of the nasal reaction to histamine; (2) inflammatory cells in nasal lavage and scraped nasal mucosal epithelium, and (3) nasal vasomotor response to cold stimulation of the feet evaluated by acoustic rhinometry., Results: Inflammatory cells were not found to be involved in idiopathic rhinitis. Nasal reactivity to histamine was significantly enhanced in patients with idiopathic rhinitis compared to normal controls, but was significantly lower compared to those with allergic rhinitis. The most prominent finding in idiopathic rhinitis was nasal mucosal swelling induced by cold stimulation of the feet. While in normal controls, cold stimulation of the feet caused mucosal contraction due to sympathetic excitation, sympathetic nasal vasomotor response in idiopathic rhinitis patients was significantly inhibited and caused mucosal swelling and enhanced nasal secretion. Mucosal reactions observed in allergic rhinitis were between those observed in idiopathic rhinitis and in normal controls. Cold stimulation of the feet increased systolic blood pressure by 5-15 mm Hg, but the degree of increase observed in the 3 groups was almost equal., Conclusions: The above findings indicate that patients with idiopathic rhinitis have abnormalities that inhibit sympathetic reactions and enhance parasympathetic vasomotor response at peripheral levels, possibly in the nasal mucosa.

IL-5 is known to be closely related to the infiltration, activation and proliferation of eosinophils. In this study, we evaluated the in vivo effects of anti-IL-5 monoclonal antibody (mAb) in the murine model of nasal allergy. The mAb treatment inhibited the antigen-induced late phase eosinophilia, but had no effects on the number of basophilic cells. It also inhibited early phase nasal symptoms, and tended to inhibit histamine hypersensitivity. These findings suggest that IL-5 plays an important role in the pathogenesis of allergic nasal disorders.

Background: A growing body of evidence suggests that proinflammatory cytokines play a role in allergic inflammation by attracting and activating inflammatory cells. In this study, we have investigated the relationship between interleukin-8 (IL-8) in nasal lavage fluid and the local activation of eosinophils and neutrophils following nasal allergen challenge of allergic patients., Methods: Nasal challenges were performed with grass pollen extract in 14 allergic patients and 5 nonallergic controls. Nasal lavage fluid was collected repeatedly for 10 h, and the levels of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were used as markers of eosinophil and neutrophil activation, respectively. The levels of these molecules were compared with that of IL-8 in nasal lavage fluid., Results: Allergen challenge of allergic patients produced a significant late-phase increase in the levels of ECP and MPO. Furthermore, the level of MPO showed a highly significant correlation with the level of IL-8 in lavage fluid (r = 0.8, p< 0.0001), whereas there was no significant relationship between the levels of ECP and IL-8., Conclusion: Interestingly, our findings suggest that both eosinophils and neutrophils are activated following nasal allergen challenge. In addition, our results are consistent with the hypothesis that IL-8 acts as a chemoattractant/activator of neutrophils during the late phase of the allergic inflammation. In contrast, we were not able to demonstrate any significant relationship between the level of IL-8 in lavage fluid and the activation of eosinophils.