Cystic fibrosis chemokines

Luminex xMAP Cardiac markers Cancer markers Metabolic markers Neurobiology Cytokines Chemokines Growth factor Gene expression profiling Nuclear receptors HLA testing Infectious disease Cystic fibrosis... 

These studies help support the concept that the environment of the cystic fibrosis airway (at least in the fetus) is different from that of normal airways. They also suggest that the airways of cystic fibrosis patients have an innate tendency toward the development of an inflammatory response. Since the production of IL-8 occurred in sterile xenografts of cystic fibrosis tracheas, the findings also support the view that a chemokine necessary for the initiation of an inflammatory response (i.e., IL-8) can be produced in the absence of infection. However, it cannot be excluded that the production of IL-8 was not due to trauma or injury to the epithelium during the creation of the xenografts. In the next section, we will review recent studies that address the events, cell types, and mechanisms responsible for in the initiation and amplification of airway inflammation in cystic fibrosis. 

Given that most adolescents and adults are chronically colonized with P. aeruginosa, attention has logically been focused on determining the role of this bacterium and its products in the production of pro-inflammatory cytokines and chemokines in normal and cystic fibrosis airway epithelia, and in epithelial cell lines established from patients with cystic fibrosis, or all lines which model the mutation of the CFTR. 

While it is abundantly clear that pro-inflammatory cytokines and chemokines are present in elevated levels in the airways of patients with cystic fibrosis, the pattern of expression of the anti-inflammatory cytokines IL-10 and TGFP is less consistently apparent. IL-10 may be particularly important in the protection of the airways against inflammation. Originally shown to be produced in macrophages and... 

In summary, the collective findings of reduced IL-10 expression and reduced TGFp responsiveness in cystic fibrosis suggest important ways in which the production of pro-inflammatory chemokines, especially IL-8, may be augmented in the airways of cystic fibrosis patients. First, the lack of IL-10 production, and possibly TGFp, can be expected to directly contribute to increased chemokine production since in their absence, an important mechanism for suppressing pro-inflammatory chemokine production is, in essence, removed. Second, studies in TGFP-nuU mice have emphasized the importance of this molecule. 

While changes in the expression of pro- and anti-inflammatory cytokines and chemokines are clearly important in the initiation and maintenance of the inflammatory response in the airways, neutrophils also play a key role in the amplification of the inflammatory response. Neutrophils contribute to airway inflammation in several active ways, including the production of oxygen free radicals, the secretion of granule-associated enzymes (including neutrophil elastase), and the production of pro-inflammatory cytokines and chemokines (reviewed in 117). BAL studies of patients with cystic fibrosis have revealed the presence of abundant levels of neutrophil elastase, both complexed with a 1-antiprotease and as free elastase, compared to control subjects (70,118,119). 

Advances in the chemokine field have serendipitously had an impact on other fields of investigation such as asthma, chronic bronchitis, chronic obstructive pulmonary disease, cystic fibrosis, and acute respiratory distress syndrome. 

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