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 ovalbu-min-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 14th day) and challenge (i.n. on the 21st and 22nd days). In contrast, the treatment drug TLR3/dsRNA complex inhibitor-calbiochem was given on the 21st and 22nd 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, lung-body weight (LW/BW) index, airway hyperresponsiveness (AHR), and lung tissue damage sug-gest exacerbations in mice airways. On the other hand, TLR3/dsRNA complex inhibitor-calbio-chem and dexamethasone significantly reversed these changes toward normal levels.

Conclusions:These results suggest that the novel compound TLR3/dsRNA complex inhibitor-calbiochem has a better therapeutic role than dexamethasone for managing inflammatory char-acteristics in asthmatic mice lungs and is a potent target for viral asthma exacerbations