Increased Numbers of Macrophages and Neutrophils are Associated with Decreased Interleukin-33 (IL-33) Levels in Asthmatic Sputum

Abstract

RATIONALE: IL-33 is a newly described member of the IL-1 cytokine family that is constitutively expressed in endothelium and epithelium and is important in TH2 inflammation, as well as anaphylaxis. Our objective was to investigate the relationship between IL-33 and inflammatory cells in respiratory secretions from asthmatics.METHODS: Sputa from 100 Severe Asthma Research Program (SARP) subjects were collected along with demographic and clinical information. Sputum supernatants were analyzed for IL-33 (ELISA) and total protein (BCA microassay). Total and differential cell counts were also obtained. Data not meeting normal distribution tests were log transformed before standard statistical analyses including linear regressions.RESULTS: We observed a significant negative association between IL-33 pg/mg total protein and the percentage of neutrophils (R=-0.27, p=0.013), and conversely, a significant positive association for the percentage of macrophages (R=0.26, p=0.02). However, a significant negative association was observed between IL-33 pg/mg total protein and actual macrophage numbers (R=-0.35, p=0.002) and a trend towards a significant negative association between IL-33 and actual neutrophil count (R=-0.20, p=0.07). Corresponding to the negative association of IL-33 with percent and actual number of neutrophils, there was also a significant negative association with IL-8, a neutrophil-relevant cytokine (R=-0.42, p=0.008).CONCLUSION: Increased numbers of macrophages and neutrophils appear to be associated with decreased release of IL-33 into asthmatic sputum. We hypothesize that this may be due to increased metabolism of IL-33 or release of other mediators by these cells, for example IL-8, which suppress IL-33 release. RATIONALE: IL-33 is a newly described member of the IL-1 cytokine family that is constitutively expressed in endothelium and epithelium and is important in TH2 inflammation, as well as anaphylaxis. Our objective was to investigate the relationship between IL-33 and inflammatory cells in respiratory secretions from asthmatics. METHODS: Sputa from 100 Severe Asthma Research Program (SARP) subjects were collected along with demographic and clinical information. Sputum supernatants were analyzed for IL-33 (ELISA) and total protein (BCA microassay). Total and differential cell counts were also obtained. Data not meeting normal distribution tests were log transformed before standard statistical analyses including linear regressions. RESULTS: We observed a significant negative association between IL-33 pg/mg total protein and the percentage of neutrophils (R=-0.27, p=0.013), and conversely, a significant positive association for the percentage of macrophages (R=0.26, p=0.02). However, a significant negative association was observed between IL-33 pg/mg total protein and actual macrophage numbers (R=-0.35, p=0.002) and a trend towards a significant negative association between IL-33 and actual neutrophil count (R=-0.20, p=0.07). Corresponding to the negative association of IL-33 with percent and actual number of neutrophils, there was also a significant negative association with IL-8, a neutrophil-relevant cytokine (R=-0.42, p=0.008). CONCLUSION: Increased numbers of macrophages and neutrophils appear to be associated with decreased release of IL-33 into asthmatic sputum. We hypothesize that this may be due to increased metabolism of IL-33 or release of other mediators by these cells, for example IL-8, which suppress IL-33 release.