Production of the potent neutrophil chemokine, growth-related protein α (GRO α), is not elevated in cystic fibrosis children

Abstract

Progressive neutrophil-mediated lung damage causes much of the morbidity and mortality in cystic fibrosis (CF). Neutrophil chemoattractants implicated in CF include interleukin (IL-)8, tumour necrosis factor (TNFα ) and leukotriene (LT)B4, but growth-related protein α (GRO α), a highly potent neutrophil chemokine, has not been investigated. Atopic status has been considered to contribute to the marked heterogeneity of pulmonary disease in CF. We hypothesized that GRO α may be produced in biologically-significant amounts in the CF lung, and that enhanced production of GRO α, IL-8 or LTB4may contribute to the poorer lung function seen in atopic CF patients compared to non-atopic CF patients. GRO α, IL-8 and LTB4levels in the sputum of atopic and non-atopic CF patients were assessed by immunoassays, and GRO α and IL-8 levels were also assessed in the plasma of CF patients and normal controls. As expected, there were high levels of IL-8 and LTB4in most CF sputum samples, and IL-8 levels were higher in CF plasma than in control plasma (P=0·02). In contrast, GROα was undetectable (<5 pg ml−1) in the sputum of 21 out of 25 CF patients, with low levels (range 144–825 pg ml−1) in the remainder, and median levels of GRO α in CF plasma (33 pg ml−1, n=24) were not significantly different from controls (34 pg ml−1,n =25). Lung function [forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC)] was significantly poorer in atopic CF compared to non-atopic CF patients (P<0·02), but sputum levels of GRO α, IL-8 and LTB4were not different between the subgroups. Our results suggest that unlike LTB4and IL-8, GRO α does not contribute to neutrophilic inflammation in the CF lung, and other factors must determine the impaired lung function observed in atopic CF patients. These results may have important implications in the development of chemokine receptor antagonists as novel anti-inflammatory agents in CF.