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.
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.
authors.affiliation: Department of Microbiology, Panjab University, Chandigarh 160014, India. vij_tox@yahoo.com
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.forename: Kusum
authors.initials: K
authors.lastname: Harjai
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chhibber
mesh_terms: D015762:2-Chloroadenosine / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000032:analysis; D004359:Drug Therapy, Combination / Q000379:methods; D007155:Immunologic Factors / Q000627:therapeutic use*; D007711:Klebsiella pneumoniae / Q000276:immunology / Q000472:pathogenicity*; D008168:Lung / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000517:prevention & control*; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D007155:Immunologic Factors; D015762:2-Chloroadenosine