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Research Article

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

Author(s): Swamita Arora, Mohit Agrawal, Kantrol Kumar Sahu, Sanjar Alam, Wasim Akram, Mohammad Khalid, Shivendra Kumar*, Sunam Saha, Kuldeep Singh and Hema Chaudhary

Volume 22, Issue 3, 2024

Published on: 19 January, 2024

Article ID: e190124225826 Pages: 11

DOI: 10.2174/0122113525282849231228125935

Price: $65

Abstract

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 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, 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.

Graphical Abstract

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