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Background The pathophysiologic mechanism of allergy is dependent on the action of many redox-sensitive proinflammatory mediators. However, even though redox disturbances are believed to be a hallmark of inflammation, little is known of the effect of redox imbalance to the pathophysiology of allergic rhinitis. We thus opted to investigate the relation of oxidative stress and allergic rhinitis, through the utilization of a potent antioxidant substance (N-acetylcysteine [NAC]) in a rat model of allergic rhinitis and the evaluation of its action on specific markers of inflammation. Methods NAC (50 mg/kg and 250 mg/kg) was intraperitoneally administered to ovalbumin (OVA)-sensitized rats prior to intranasal challenge with OVA. Mucosal congregation of inflammatory cells (eosinophils and mast cells), mucosal expression of redox-sensitive enzymes (inducible nitric oxide synthase [iNOS] and cyclooxygenase 2 [COX-2]), and the blood levels of a key proinflammatory mediator (tumor necrosis factor-alpha [TNF-alpha]) were evaluated. Results Intranasal OVA challenges lead to mucosal inflammation, induction of the mucosal expression of iNOS and COX-2 and elevation of TNF-alpha blood levels. NAC significantly inhibited accumulation of inflammatory cells and downregulated iNOS expression and TNF-alpha serum levels. The role of COX-2 appeared to be 2-fold and its expression was divergently modulated by NAC. Conclusion Our findings suggest that redox balance is involved in the pathophysiology of allergic rhinitis in rats and that NAC can potentially suppress the allergen-induced nasal inflammatory cascade. The investigation of the role of oxidative stress in atopy could help in the evaluation of the therapeutic potential of antioxidant substances in allergic diseases. (C) 2013 ARS-AAOA, LLC.

Conventional experimental models of respiratory allergy have contributed greatly to our current knowledge of the pathophysiology of allergic airway diseases; nevertheless, they are contingent upon unnatural sensitization techniques, entailing adjuvant-aided intraperitoneal (i.p) administration of antigen. Currently, there is a growing appreciation of the impact of tolerance mechanics in the pathophysiology of respiratory allergy. Thus, inasmuch as adjuvants exert a robust tolerance-modifying action, a transition from the conventional method of experimental sensitization to one that is more naturally and clinically relevant becomes important. We therefore opted to survey the literature and identify agents that could interfere with sensitization mechanics following non-adjuvant-aided airway exposure of laboratory rodents to aeroallergen. GM-CSF was found to exert robust Th-2-polarizing action in this setting. Conversely, IL-10 fulfilled an important, albeit not so clear-cut, tolerance-favoring role; TGF-beta was also identified as a likely instigator of tolerogenesis. The role of Notch signaling in the sensitization versus tolerance dilemma appeared to be important but diverse. Collectively, these factors appeared to profoundly and diversely modulate the balance between tolerance and sensitization in naturally relevant experimental models of allergic airway disease.

Asthma is a heterogeneous disease more appropriately seen as a syndrome rather than a single pathologic entity. Although it can remain quiescent for extended time periods, the inflammatory and remodeling processes affect the bronchial milieu and predispose to acute and occasionally severe clinical manifestations. The complexity underlying these episodes is enhanced during childhood, an era of ongoing alterations and maturation of key biological systems. In this review, the authors focus on such sudden-onset events, emphasizing on their diversity on the basis of the numerous asthma phenotypes.