Responsiveness of blood and sputum inflammatory cells in Japanese COPD patients, non-COPD smoking controls, and non-COPD nonsmoking controls

Abstract

Purpose

To compare pulmonary and systemic inflammatory mediator release, pre- and poststimulation, ex vivo, in cells from Japanese patients with chronic obstructive pulmonary disease (COPD), non-COPD smoking controls, and non-COPD nonsmoking controls (NSC).

Patients and methods

This was a nontreatment study with ten subjects per group. Inflammatory biomarker release, including interleukin (IL)-6 and -8, matrix metalloproteinase-9, and tumor necrosis factor (TNF)-α, was measured in peripheral blood mononuclear cells (PBMC) and sputum cells with and without lipopolysaccharide or TNF-α stimulation.

Results

In PBMC, basal TNF-α release (mean ± standard deviation) was significantly different between COPD (81.6±111.4 pg/mL) and nonsmoking controls (9.5±5.2 pg/mL) (P<0.05). No other significant differences were observed. Poststimulation biomarker release tended to increase, with the greatest changes in the COPD group. The greatest mean increases were seen in the lipopolysaccharide-induced release of matrix metalloproteinase-9, TNF-α, and IL-6 from PBMC. Pre- and poststimulation data from sputum samples were more variable and less conclusive than from PBMC. In the COPD group, induced sputum neutrophil levels were higher and macrophage levels were lower than in either control group. Significant correlations were seen between the number of sputum cells (macrophages and neutrophils) and biomarker levels (IL-8, IL-6, and TNF-α).

Conclusion

This was the first study to compare cellular inflammatory mediator release before and after stimulation among Japanese COPD, smoking controls, and nonsmoking controls populations. Poststimulation levels tended to be higher in patients with COPD. The results suggest that PBMC are already preactivated in the circulation in COPD patients. This provides further evidence that COPD is a multicomponent disease, involving both airway and systemic inflammation.

Keywords:

• chronic obstructive pulmonary disease
• lipopolysaccharide
• peripheral blood mononuclear cells
• sputum
• tumor necrosis factor-α

Supplementary material

Table S1 Summary of biomarkers in peripheral blood mononuclear cells (stimulated by TNF-α or LPS)

Acknowledgments

Funding for this study was provided by GlaxoSmithKline. The authors would like to thank the following people for their contributions: members of Kurume University who participated in subject recruitment – Kyoko Yamaguchi and Emiko Kuma for performing the biomarker analyses. The authors would also like to thank the following: members of the GlaxoSmithKline team who developed the study protocol – Etsuko Hayashi, Hideo Kikkawa, and Daisuke Yoshimoto; and The Institute of Japanese Union of Scientists & Engineers for performing the data management and statistical analysis. Medical writing and editorial support in the form of development of draft outline, development of manuscript (all drafts), assembling tables, and collating author comments was provided by Dr Kathryn White of Cathean Ltd, and was funded by GlaxoSmithKline.

Author contributions

All authors were involved in the acquisition and analysis of data, drafting and critical revision of the manuscript, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

Akihiro Kobayashi and Tomoyuki Hayamizu were employees of GlaxoSmithKline at the time of conducting the study, and report no other relationships or activities that could appear to have influenced the submitted work. Tomoaki Hoshino discloses that his university (Kurume University) has received research grants from GlaxoSmithKline, who sponsored the study. Kazuko Matsunaga reports no conflicts of interest in this work. Takashi Kinoshita discloses his university (Kurume University) has received research grants from GlaxoSmithKline, who sponsored the study. Tomotaka Kawayama discloses having received honoraria/consulting fees from GlaxoSmithKline for participating in advisory board meetings and his university (Kurume University) has received research grants from GlaxoSmithKline, who sponsored the study. Malcolm Johnson is an independent respiratory consultant employed by GlaxoSmithKline to help in the design and conduct of the study. Malcolm Johnson is a shareholder in GlaxoSmithKline, but has no other relationships or activities that could appear to have influenced the submitted work. The authors report no other conflicts of interest in this work.