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Critical Care

Volume 17 Supplement 4

Sepsis 2013

Open Access

Potential anti-inflammatory role of 2-chloroadenosine treatment during acute lung inflammation in BALB/c mice suffering from Klebsiella pneumoniae B5055-induced acute lung infection

  • Vijay Kumar1,
  • Kusum Harjai1 and
  • Sanjay Chhibber1
Critical Care201317(Suppl 4):P68

https://doi.org/10.1186/cc12967

Published: 5 November 2013

Keywords

Klebsiella PneumoniaeNeutrophil InfiltrationImmunomodulatory AgentLung HomogenateAcid Aspiration

Background

Acute lung inflammation (ALI) is a life-threatening pathology and can develop during the course of several clinical conditions such as pneumonia, acid aspiration or sepsis. Adenosine plays a significant role in controlling acute inflammation via binding to A2A receptors on inflammatory cells; that is, neutrophils or macrophages. The present study was designed to evaluate the anti-inflammatory and immunomodulatory effects of 2-chloroadenosine (2-CADO), alone or in combination with amoxicillin/clavulanic acid (AMC), in Klebsiella pneumoniae B5055-induced acute lung infection in mice.

Materials and methods

Acute lung infection in mice was induced by directly instilling the selected dose (104 colony-forming units/ml) of bacteria intranasally. Histopathological examination of the lungs was performed to reveal neutrophil infiltration into the lung alveoli. In addition to the major proinflammatory cytokines TNFα and IL-1α, levels of the anti-inflammatory cytokine IL-10 were also determined by ELISA.

Results

Intranasal instillation of bacteria caused profound neutrophil infiltration into the lung alveoli as well as a significant increase in the levels of proinflammatory mediators (that is, TNFα and IL-1α). However, intravenous administration of 2-CADO 10 μg/kg/day, alone or in combination with an antibiotic (that is, AMC 20 μg/ml/day i.p. 1 day after establishment of infection), significantly decreased neutrophil infiltration into the lung alveoli. A significant decrease in TNFα and IL-1α along with elevation of IL-10 levels in the lung homogenate of mice with acute lung infection was observed upon treatment with 2-CADO alone, with no significant decrease in bacterial counts. Moreover in combination with AMC, 2-CADO exhibited its immunomodulatory action in acute lung infection and prevented ALI observed during acute bacterial pulmonary infection, whilst an antibacterial action was exhibited by AMC.

Conclusions

2-CADO proved a potent immunomodulatory agent during acute Gram-negative bacteria-induced ALI and exhibited its anti-inflammatory and immunomodulatory potential even in the presence of antibiotics. Thus, it has a potential to be used as an adjunct immunomodulatory agent during acute inflammatory conditions like ALI or sepsis.

Authors’ Affiliations

(1)
Department of Microbiology, Panjab University, Chandigarh, India

Copyright

© Kumar et al.; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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