Endocrine Abstracts

Introduction: C-reactive protein (CRP), an acute reactant protein and member of the pentraxins family has a primitive defense function against exogenous organisms. Although its production is predominantly under the control of IL-6, IL-1 and tumor necrotic factor also contribute to hepatic synthesis and CRP secretion. CRP is mainly produced in the liver and possibly other tissues, such as atherosclerotic lesions. C-reactive protein (CRP) is associated with increased risk for cardiovascular diseases (CVD), while increased serum uric acid level is suggested to be independently associated with an increased risk of CVD. Accordingly, in the present study, we compared serum CRP levels between healthy controls and patients with gout who were matched in regard to parameters associated with serum CRP levels. In addition, since benzbromarone decreases the level of urate in serum, based on its uricosuric action and activates peroxisome proliferater-activated receptor alpha (PPARalpha), we also examined whether benzbromarone had effects on serum CRP levels in patients with gout and the expression of the messenger mRNA in hepatoma cell line, HuH7.

Methods: In the first experiment, blood samples were drawn from 40 healthy males and 40 male patients with gout after an overnight fast. In the second experiment, 42 male patients with gout were given uric acid-lowering therapy with benzbromarone. Blood samples were drawn after an overnight fast before and 1 year after beginning benzbromarone treatment. In the third experiment, the effects of benzbromarone on IL1beta-induced CRP expression were determined in HuH7 cells

Results: Serum CRP levels were not significantly different between the patients with gout and healthy subjects, while serum CRP levels were decreased by 11% after benzbromarone treatment, as compared to the values before treatment (P<0.01). In addition, our in vitro findings suggested that benzbromarone, as well as fenofibrate, down-regulated IL1beta-stimulated CRP gene expression via PPARalpha pathway.

Conclusions: These results suggest that hyperuricemia may not contribute to an increase in serum CRP level, while benzbromarone may have a favorable effect on CRP.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.