Ha. Wyatt et al., Production of the potent neutrophil chemokine, growth-related protein alpha (GRO alpha), is not elevated in cystic fibrosis children, RESP MED, 94(2), 2000, pp. 106-111
Progressive neutrophil-mediated lung damage causes much of the morbidity an
d mortality in cystic fibrosis (CF). Neutrophil chemoattractants implicated
in CF include interleukin (IL-)8, tumour necrosis factor (TNF alpha) and l
eukotriene (LT)B-4, but growth-related protein alpha (GRO alpha), a highly
potent neutrophil chemokine, has not been investigated. Atopic status has b
een considered to contribute to the marked heterogeneity of pulmonary disea
se in CF. We hypothesized that GRO alpha may be produced in biologically-si
gnificant amounts in the CF lung, and that enhanced production of GRO alpha
, IL-8 or LTB4 may contribute to the poorer lung function seen in atopic CF
patients compared to non-atopic CF patients. GRO alpha, IL-X and LTB4 leve
ls in the sputum of atopic and non-atopic CF patients were assessed by immu
noassays, and GRO alpha 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 LTB4 in most CF sputum samples, and IL-g levels were higher in CF pl
asma than in control plasma (P=0.02). In contrast, GRO alpha was undetectab
le (< 5 pg ml(-1)) in the sputum of 21 out of 25 CF patients, with low leve
ls (range 144-825 pg ml(-1)) in the remainder, and median levels of GRO alp
ha 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 I
sec (FEV1) and forced vital capacity (FVC)] was significantly poorer in at
opic CF compared to non-atopic CF patients (P<0.02), but sputum levels of G
RO alpha, IL-8 and LTB4 were not different between the subgroups. Our resul
ts suggest that unlike LTB4 and IL-gl GRO alpha does not contribute to neut
rophilic inflammation in the CF lung, and other factors must determine the
impaired lung function observed in atopic CF patients. These results may ha
ve important implications in the development of chemokine receptor antagoni
sts as novel anti-inflammatory agents in CF. (C) 2000 HARCOURT PUBLISHERS L
TD.