Abstract
Rationale
IL-6 is a pleiotropic cytokine that is involved in the regulation of inflammation. Increased serum IL-6 levels are associated with reduced FEV1 in COPD patients independent of age or smoking status. Elevated levels of sputum IL-6 in COPD patients have been associated with increased exacerbation frequency. The mechanism by which IL-6 may mediate inflammation in COPD is uncertain. We sought to determine levels of IL-6 and its soluble receptor (sIL-6R) in COPD sputum. IL-6 signaling can alter the levels of the neutrophil chemoattractant CCL3 and the monocyte chemoattractant CCL2; we also investigated the levels of these chemokines.
Methods
70 patients with GOLD stage I-IV COPD and 30 healthy controls comprising of 15 healthy smokers (HS) and 15 healthy non-smokers (HNS) underwent sputum sampling with PBS processing. Levels of IL-6, sIL-6R, CCL2, CCL3 were determined by multiplex analysis (MSD® platform) of sputum supernatant.
Results
Healthy smokers expressed the highest levels of sputum IL-6. COPD patients expressed the highest levels of sIL-6R. COPD patients also expressed the highest levels of sputum CCL3. In contrast, CCL2 expression was significantly reduced in COPD patients.

 COPDHSHNSANOVA
IL-6 (pg/ml)116.8 (84.5)258.3 (214.1)80.87 (74.34)p=0.0016
sIL-6R (pg/ml)256.6 (260.9)98.84 (44.33)136.2 (90.31)p=0.019
CCL2 (pg/ml)26.7 (51.2)207.8 (104)162.4 (142.6)p<0.0001
CCL3 (pg/ml)182.1 (164)8.12 (6.83)58.75 (63.17)p<0.0001
Data expressed as mean (SD)


Conclusion
We report evidence of enhanced IL-6 signaling and CCL3 activity in COPD sputum. We have observed that there is reduced CCL2 activity and enhanced CCL3 activity in COPD sputum. IL-6 may therefore promote neutrophillic inflammation in COPD through up-regulation of CCL3 expression.