Adenosine-mediated immunomodulatory action on alveolar macrophages during Klebsiella pneumoniae B5055 induced acute lung infection

Abstract

Background: Adenosine is considered as a potent metabokine with potential immunoregulatory and immunomodulatory function. It is produced during conditions causing metabolic stress including hypoxia and inflammation. However, tissue damage during acute infections including, sepsis also causes a systemic increase in its level. Methods and materials: In the current study, we have investigated the effect of 2-cholroadenosine (2-CADO) on the pulmonary innate immune response during acute lung infection induced by Klebsiella pneumoniae B5055. Acute lung infection causing acute lung inflammation or injury (ALI) was induced by intranasal instillation of a selected dose of K. pneumoniae B5055 into mice. Subsequently, mice were treated with 2-CADO (10 μg/kg/day/iv) using a treatment schedule. Mice were observed for mortality and other inflammatory damage. Pro-inflammatory (TNF-α, IL-1α) and anti-inflammatory cytokines (IL-10) were measured by ELISA as per the manufacturer's instructions. The alveolar macrophage-mediated phagocytosis of the bacteria was measured in terms of phagocytic uptake and intracellular killing. Also, other biochemical parameters including, nitric oxide (NO.) and hydrogen peroxide (H2O2) were also measured in the bronchoalveolar lavage fluid (BALF). Histopathological analysis of the lungs was performed to observe inflammatory damage to the lungs. Results: No mortality was observed in both the control and treated groups. 2-CADO treatment modulated the pro-inflammatory function of alveolar macrophages by significantly (p≤0.05) decreasing their phagocytic activity (both phagocytic uptake and intracellular killing of the pathogen), nitric oxide (NO) and hydrogen peroxide (H2O2) release. 2-CADO also significantly (p ≤ 0.05) decreased the neutrophil infiltration into the lungs. Levels of pro-inflammatory cytokines (IL-1α and TNF-α) were decreased significantly (p ≤ 0.05) decreased. However, levels of IL-10 were found to be significantly (p ≤ 0.05) elevated. Conclusion: Adenosine, a metabokine has promising immunomodulatory action during gram-negative bacterial pneumonia and associated inflammation.