Peripheral blood neutrophil and G-CSF levels are linked to aztreonam lysine use in humans with cystic fibrosis

Abstract

Abstract The neutrophil response contributes substantially to disease progression in cystic fibrosis (CF). Research was directed at understanding the circulating neutrophil in CF. Medical chart data and 30 blood samples were collected from volunteers with CF (ΔF508/ΔF508; mean age 29 years) while 21 blood samples were collected from age-matched controls. Isolated plasma was then analysed for G-CSF and CXCL1 and statistically compared with neutrophil numbers and medical chart data, while signalling pathways in these neutrophils were investigated using kinome array approaches. Our results indicated that the CF group being treated with the inhaled β-lactam antibiotic aztreonam lysine had significantly increased G-CSF levels (p<.05) and isolated circulating neutrophil numbers (p<.01) when compared to the CF group without the antibiotic. Neutrophil numbers were also significantly increased in both the inhaled aztreonam lysine positive (p<.001) and negative (p<.05) CF groups when compared to the non-CF control group. Neutrophil numbers in CF displayed a significant (p<.05) positive correlation with G-CSF levels. We observed a significant (p<.05) negative correlation between disease progression in CF (observed as FVC%) and neutrophil numbers. Kinome analyses indicated several altered pathways that warrant further investigation. These results revealed a connection in CF between antibiotic treatment, inflammatory markers in the blood, altered neutrophil signaling, changes in circulating neutrophil numbers, and disease progression. From a clinical perspective these results identified a potential connection between inhaled aztreonam lysine, circulating neutrophil numbers and decreased lung function in our CF volunteers.