Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum |
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Authors: | Arjun K Ravi Shruti Khurana Jonathan Lemon Jonathan Plumb George Booth Louise Healy Matthew Catley J?rgen Vestbo Dave Singh |
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Affiliation: | .Medicines Evaluation Unit, University Hospital of South Manchester NHS Foundation Trust, University of Manchester, Manchester, UK ;.Manchester Academic Health Science Centre; University Hospital South Manchester NHS Foundation Trust; NIHR Respiratory and Allergy Clinical Research Facility, University of Manchester, Manchester, UK ;.UCB, Slough, Berkshire UK ;.Department of Cardiology and Respiratory Medicine, Hvidovre Hospital and University of Copenhagen, Copenhagen, Denmark |
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Abstract: | BackgroundCOPD patients have increased numbers of macrophages and neutrophils in the lungs. Interleukin-6 (IL-6) trans-signaling via its soluble receptor sIL-6R, governs the influx of innate immune cells to inflammatory foci through regulation of the chemokine CCL3. We hypothesized that there would be enhanced levels of IL-6, sIL-6R and CCL3 in COPD sputum.Methods59 COPD patients, 15 HNS and 15 S underwent sputum induction and processing with phosphate buffered saline to obtain supernatants for IL-6, sIL-6R and CCL3 analysis. Cytoslides were produced for differential cell counting and immunocytochemistry (COPD; n = 3) to determine cell type surface expression of the CCL3 receptors CCR5 and CCR1.ResultsCOPD patients expressed higher levels (p < 0.05) of sIL-6R and CCL3 compared to controls (sIL-6R medians pg/ml: COPD 166.4 vs S 101.1 vs HNS 96.4; CCL3 medians pg/ml: COPD 117.9 vs S 0 vs HNS 2.7). COPD sIL-6R levels were significantly correlated with sputum neutrophil (r = 0.5, p < 0.0001) and macrophage (r = 0.3, p = 0.01) counts. Immunocytochemical analysis revealed that CCR5 and CCR1 were exclusively expressed on airway macrophages.ConclusionEnhanced airway generation of sIL-6R may promote IL-6 trans-signaling in COPD. Associated upregulation of CCL3 may facilitate the recruitment of macrophages into the airways by ligation of CCR1 and CCR5.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0103-4) contains supplementary material, which is available to authorized users. |
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Keywords: | COPD Sputum Two-step sputum processing Interleukin-6 sIL-6R CCL3 |
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