Interleukin-6 neutralization alleviates pulmonary inflammation in mice exposed to cigarette smoke and poly I:C

Increased systemic and pulmonary levels of interleukin-6 (IL-6) are associated with the severity of exacerbations and decline of lung function in patients with chronic obstructive pulmonary disease (COPD). Whether IL-6 is directly involved or plays a bystander role in the pathophysiology of COPD remains unclear. Here we hypothesized that neutralizing circulating levels of IL-6 would modulate episodes of acute pulmonary inflammation following cigarette smoke (CS) exposure and virus-like challenges. For this purpose, we used a model where C57BL/6 mice were exposed to CS twice daily via a nose-only system, and concomitant periodic intranasal challenge with polyinosine-polycytidylic acid (poly I:C), a synthetic ligand for Toll Like Receptor-3 that mimics the encounter with double stranded RNA that is carried by influenza-like viruses. This protocol recapitulates several aspects of acute pulmonary inflammation associated with COPD, including prominent airway neutrophilia, insensitivity to steroid treatment, and increased levels of several inflammatory cytokines in bronchoalveolar lavage (BAL) samples. While IL-6 deficient mice exposed to CS/poly I:C developed pulmonary inflammation similarly to wild-type (WT) controls, WT mice exposed to CS/poly I:C and treated intraperitoneally with IL-6 neutralizing antibodies showed significantly lower blood counts of lymphocytes and monocytes, lower BAL levels of IL-6 and CXCL1/KC, as well as reduced numbers of BAL neutrophils, lymphocytes and...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research