has been shown to begin at a very early stage in infants with CF and inflammation
has been detected in BAL fluid taken from asymptomatic infants with CF within
weeks of birth (Armstrong et al,
2005). Indeed, a study by Pfeffer et al which cultured blood monocytes from CF
adults and healthy controls in heterologous serum, which acted to remove the
influence of any stimuli, found increased tumour necrosis factor alpha (TNF- ?) release from these monocytes (7).
Additionally, a study of a G551D mouse model by Thomas et al reported monocytes
which exhibit hypersensitivity to lipopolysaccharide (LPS) and increased TNF-
? of this CF mouse model
when compared to wild-type mice (8). Both of these studies suggest that the CF
airways are intrinsically ‘pro-inflammatory’, potentially before the first exposure
to bacterial infection and provides evidence that the pathology of CF is
related not only to an immune response to pathogens and other inflammatory
stimuli but also the abnormal regulation of the immune system.
studies have been carried out to investiagate the inflammatory response and
whether inflammation arises in infants with CF without prior or present
infection. One study by Rosenfeld et al measured
cytokine levels in BAL fluid from infants with CF aged 1.5-71 months, with this
study showing an inflammation characterised by increased levels of
pro-inflammatory cytokine interleukin 8 (IL-8, a principle neutrophil
chemoattractant in the lung) and a higher neutrophil density in the BAL fluid
in both the presence and absence of lower airway pathogens (Rosenfeld, 2001). A
further study by Thursfield et al
showed that in infants up to 4 months of age, when compared to healthy
controls, BAL fluid cell count and neutrophil differential count was increased
in infants with CF and who were asymptomatic and culture negative. These studies
suggests, among many others, that in early CF inflammation may indeed be
present without the presence of infection (Thursfield et al, 2012).
of the origins of inflammation in early CF, infection occurs very rapidly after
birth and the inflammatory response to these pathogens is exaggerated and
severe (Cantin et al, 2015).