Abstract Text: Viral respiratory infections trigger severe exacerbations of asthma, worsen disease symptoms, and impair lung function. Poly (I:C), a structural mimic of double-stranded RNA, is commonly used to study immune responses linked to respiratory viral infections. The current study seeks to assess the impact of poly (I:C) on asthma exacerbations. Female BALB/c mice were sensitized and challenged with Ovalbumin (OVA), followed by intranasal administration of poly (I:C). Dexamethasone was administered intraperitoneally before poly (I:C) instillation. Mice were assessed for airway hyperresponsiveness (AHR) and lung inflammation. OVA exposure resulted in steep increase in BALF inflammatory cells, particularly eosinophils. Intriguingly, poly (I:C) at a dose of 200μg augmented lung inflammation in OVA-exposed mice. Qualitative analysis of BALF cells revealed that while the number of eosinophil was decreased but the neutrophils number were increased substantially upon poly (I:C) exposure in OVA challenged mice. Additionally, mice exposed to OVA/poly (I:C) developed AHR as reflected by an increase in sRaw. Next, dexamethosome failed to ameliorate Poly (I:C) induced asthma exacerbation. It appears that switch in inflammatory response from eosinophils to neutrophils may be responsible for failure of dexamethasone under the condition. Further, analysis of Th2/Th1 panel cytokines show that poly (I:C) modulates the immune response from Th2 towards Th1 phenotype. Overall, our data suggests major shift in immune response during poly(I:C) mediated asthma exacerbation makes the condition steroid refractory in nature.
