© 2007 American Thoracic Society
C-reactive Protein—Marker of Inflammation or Future Therapeutic Target?To the Editor:In his recent editorial, Donaldson discusses the large body of work linking systemic inflammation and chronic obstructive pulmonary disease (COPD) (1). He also reminds us that systemic inflammation and C-reactive protein (CRP) levels have been associated with reduced lung function and diminished muscle strength and 6-minute walking distances. However, he recommends caution when linking CRP with COPD outcome, emphasizing that CRP rises in many inflammatory conditions and therefore is not specific for COPD. We agree with the point that CRP is currently not a predictor of COPD from a purely statistical viewpoint, but feel that with time this will change and that CRP will be shown to have a more direct role in inflammatory lung disease. This opinion is fueled by the knowledge surrounding the potential mode of action of CRP. CRP binds to phosphocholine receptors and to a number of autologous ligands, including plasma lipoproteins (2), apoptotic cells (3), and damaged cell membranes (4). CRP also binds extrinsic ligands, including glycan and phospholipid components of microorganisms as well as capsular components of bacteria, fungi, and parasites (5). In vitro studies have shown that CRP can activate the classical complement cascade and induce the synthesis of inflammatory cytokines such as interleukin (IL)-6 and IL-8. CRP also up-regulates chemokines and adhesion molecules (5). These factors can collectively augment the initial inflammatory signal triggered by insults such as infection, inflammation, and ischemia leading to an exacerbation of tissue damage and more severe disease (5). The strong association of CRP with prognosis suggests that CRP contributes directly to the pathogenesis of certain diseases. A definitive way to test this hypothesis has been unveiled with the use of novel compounds that specifically block CRP ligand binding and its proinflammatory effects in vivo. Pepys and coworkers recently tested one of these compounds. A small molecule inhibitor of CRP was introduced to rats undergoing myocardial infarction and was found to abrogate the increase in infarct size and cardiac dysfunction produced by injection of human CRP (6). Given these findings, one can speculate that decreasing the amount of CRP binding in damaged lung tissue (thus reducing the proinflammatory stimulus) may result in reduced inflammation and improvement in lung function with a better outcome for the patient. Clearly, further animal and clinical studies are required, but it is a real possibility that, with time, we will go from "bench to bedside," progressing from monitoring CRP levels in the laboratory to treating CRP levels in the patient.
Northern General Hospital, Sheffield, United Kingdom FOOTNOTES Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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