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Interleukin-6 neutralization alleviates acute exacerbation-like disease in a model of cigarette smoke-induced pulmonary inflammation

Increased systemic and pulmonary levels of interleukin (IL)-6 have been associated with the severity of acute exacerbations and accelerated decline of lung function in COPD patients. The demonstration that IL-6 plays a pivotal role in AE-related pulmonary symptoms and therefore represents a therapeutic target for the treatment of COPD, remains elusive. We used a murine model where C57BL/6 female mice are exposed to cigarette smoke (CS) twice daily through a nose-only system, while being punctually challenged intranasally with poly I:C, a synthetic ligand for Toll Like Receptor-3 (TLR3). This protocol recapitulates several aspects of pulmonary inflammation as seen in acute exacerbations of COPD, including prominent airway neutrophilia as well as increased levels of type I interferon, GM-CSF, IL-6, KC, MIP-1 alpha, RANTES, and TNF-alpha in bronchoalveolar lavage (BAL) samples. Using this model, IL-6 deficient mice showed a susceptibility to CS-induced pulmonary inflammation that, overall, was comparable to that found with wild-type (WT) control mice. In contrast, using the same model with WT mice treated intraperitoneally with IL-6 neutralizing antibodies (rat IgG1, clone MP5-20F3, 25 mg/kg thrice weekly) diminished blood counts of lymphocytes (p=0.0070) and monocytes (p=0.0091), while this treatment also depleted BAL levels of IL-6 (p=0.0002) and reduced BAL levels of KC (p=0.0220). Total BAL cellularity was found to be largely decreased (p<0.0001) as well as BAL numbers of neutrophils (p=0.0031), lymphocytes (p<0.0001) and macrophages (p<0.0001), while inflammatory infiltrates seemed reduced in lung tissue sections from treated mice. Our results show that the neutralization of IL-6 largely abrogates pulmonary inflammation in CS-exposed mice, and therefore indicate that IL-6 may be a valid therapeutic target for the treatment of COPD, in particular in episodes of acute exacerbation.

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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 (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Kubera, J., Hammerman, K., Williams, C.M. et al. Interleukin-6 neutralization alleviates acute exacerbation-like disease in a model of cigarette smoke-induced pulmonary inflammation. J Inflamm 10 (Suppl 1), P33 (2013).

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  • Acute Exacerbation
  • Pulmonary Inflammation
  • Synthetic Ligand
  • Accelerate Decline
  • Airway Neutrophilia