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

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

Volume: 22 Issue: 3

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

Affiliation:

• Department of Pharmacy, Rajiv Academy for Pharmacy, Mathura, India

Keywords: Asthma, ovalbumin, toll-like receptors, viral disease, inflammation, immunity.

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 21^st and 22^nd days). In contrast, the treatment drug TLR3/dsRNA complex inhibitor-calbiochem was given on the 21st 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.

Cite this article as:

Arora Swamita, Agrawal Mohit, Sahu Kantrol Kumar, Alam Sanjar, Akram Wasim, Khalid Mohammad, Kumar Shivendra*, Saha Sunam, Singh Kuldeep and Chaudhary Hema, Effect of Toll-like Receptor-3 Antagonist on Viral Asthma Exacerbations Via a TLR3/dsRNA Complex Pathway, Anti-Infective Agents 2024; 22 (3) : e190124225826 . https://dx.doi.org/10.2174/0122113525282849231228125935