Effect of Toll-like Receptor-3 Antagonist on Viral Asthma Exacerbations Via a TLR3/dsRNA Complex Pathway

Background: The Toll-like receptor-3 (TLR3) ligand Poly(I:C) has been shown to induce a viral aggravation of severe asthma by identifying double-stranded RNA (dsRNA). This study aimed to evaluate the therapeutic role of the TLR3/dsRNA complex inhibitor-calbiochem compound in the treatment of Poly(I:C)-induced viral asthma exacerbations through the ovalbumin-induced asthma model in Swiss albino mice. Methods: Poly(I:C) and Ovalbumin drugs were injected in mice to sensitize (i.p. on 0, 7, and 14^th day) and challenge (i.n. on the 21^st and 22^nd days). In contrast, the treatment drug TLR3/dsRNA complex inhibitor-calbiochem was given on the 21^st and 22^nd days intraperitoneally within the study period. In-vivo measurements were carried out in BALF and serum for pro-inflammatory cytokines, inflammatory leukocyte counts, lactate dehydrogenase (LDH) and nitrite levels, lungs/body weight index, and lung tissue histopathology using H and E staining in mice airways. Results: High levels of cytokines (NF-κB, IL-1β, IL-5, RANTES, MIP-2, and MCP-1) are seen in groups exposed to OVA and Poly (I:C). Further, inflammatory leukocyte cell counts, lungbody weight (LW/BW) index, airway hyperresponsiveness (AHR), and lung tissue damage suggest exacerbations in mice airways. On the other hand, TLR3/dsRNA complex inhibitor-calbiochem and dexamethasone significantly reversed these changes toward normal levels. Conclusions: These results suggest that the novel compound TLR3/dsRNA complex inhibitorcalbiochem has a better therapeutic role than dexamethasone for managing inflammatory characteristics in asthmatic mice lungs and is a potent target for viral asthma exacerbations.