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  • Title: 2-Chloroadenosine (2-CADO) treatment modulates the pro-inflammatory immune response to prevent acute lung inflammation in BALB/c mice suffering from Klebsiella pneumoniae B5055-induced pneumonia.
    Author: Kumar V, Harjai K, Chhibber S.
    Journal: Int J Antimicrob Agents; 2010 Jun; 35(6):599-602. PubMed ID: 20189776.
    Abstract:
    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 A(2A) receptors on inflammatory cells, i.e. 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. Acute lung infection in mice was induced by directly instilling the selected dose (10(4) 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 pro-inflammatory cytokines tumour necrosis factor-alpha (TNFalpha) and interleukin (IL)-1alpha, levels of the anti-inflammatory cytokine IL-10 were also determined. Intranasal instillation of bacteria caused profound neutrophil infiltration into the lung alveoli as well as a significant increase in the levels of pro-inflammatory mediators (i.e. TNFalpha and IL-1alpha). However, intravenous administration of 2-CADO 10 microg/kg/day, alone or in combination with an antibiotic (i.e. AMC), significantly decreased neutrophil infiltration into the lung alveoli. A significant decrease in TNFalpha and IL-1alpha 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, whilst an antibacterial action was exhibited by AMC.
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