Alterations in the Expression of the NF-κB Family Member RelB as a Novel Marker of Cardiovascular Outcomes during Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) exacerbations are acute events of worsened respiratory symptoms and enhanced inflammation partly mediated by NF-kappa B activation. RelB, an NF-kappa B family member, suppresses cigarette smoke-induced inflammation but its expression in COPD is unknown. Moreover, there is no information on its association with clinical features of COPD. The objectives of this study were to assess RelB expression relative to markers of inflammation as well as its association with cardiovascular and pulmonary features of COPD patients at stable-state and exacerbation. Methods: Data from 48 COPD patients were analyzed. Blood samples were collected from stable-state and exacerbating patients. After RNA isolation, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess RelB, Cox-2, IL-8 and IL-1 beta mRNA expression and their associations with measured clinical variables. Results: Of the 48 COPD subjects, 18 were in stable-state and 30 were in exacerbation. RelB mRNA expression was lower than that of Cox-2, IL-8, and IL-1 beta in all cases (all p<0.001, except for IL-8 at exacerbation (p = 0.22)). Cox-2, IL-8 and IL-1 beta were significantly associated with clinical features of patients in both stable-state and at exacerbation. There was no association with RelB expression and any clinical features in COPD subjects at stable-state. RelB mRNA levels were significantly associated with cardiovascular events such as systolic blood pressure during exacerbation. Conclusions: RelB mRNA expression is lower than that of the other inflammatory mediators. Expression of Cox-2, IL-8 and IL-1 beta were related to clinical features in both stable-state and at exacerbation. However, RelB expression was associated with clinical features of patients only during exacerbation, suggesting that RelB may represent a novel marker of health outcomes, in particular cardiovascular, during exacerbation in COPD.