Journal Article

Glyburide Is Anti-inflammatory and Associated with Reduced Mortality in Melioidosis

Gavin C. K. W. Koh, Rapeephan R. Maude, M. Fernanda Schreiber, Direk Limmathurotsakul, W. Joost Wiersinga, Vanaporn Wuthiekanun, Sue J. Lee, Weera Mahavanakul, Wipada Chaowagul, Wirongrong Chierakul, Nicholas J. White, Tom van der Poll, Nicholas P. J. Day, Gordon Dougan and Sharon J. Peacock

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 52, issue 6, pages 717-725
Published in print March 2011 | ISSN: 1058-4838
Published online March 2011 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1093/cid/ciq192

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Background. Patients with diabetes mellitus are more prone to bacterial sepsis, but there are conflicting data on whether outcomes are worse in diabetics after presentation with sepsis. Glyburide is an oral hypoglycemic agent used to treat diabetes mellitus. This KATP-channel blocker and broad-spectrum ATP-binding cassette (ABC) transporter inhibitor has broad-ranging effects on the immune system, including inhibition of inflammasome assembly and would be predicted to influence the host response to infection.

Methods. We studied a cohort of 1160 patients with gram-negative sepsis caused by a single pathogen (Burkholderia pseudomallei), 410 (35%) of whom were known to have diabetes. We subsequently studied prospectively diabetics with B. pseudomallei infection (n = 20) to compare the gene expression profile of peripheral whole blood leukocytes in patients who were taking glyburide against those not taking any sulfonylurea.

Results. Survival was greater in diabetics than in nondiabetics (38% vs 45%, respectively, P = .04), but the survival benefit was confined to the patient group taking glyburide (adjusted odds ratio .47, 95% confidence interval .28–.74, P = .005). We identified differential expression of 63 immune-related genes (P = .001) in patients taking glyburide, the sum effect of which we predict to be antiinflammatory in the glyburide group.

Conclusions. We present observational evidence for a glyburide-associated benefit during human melioidosis and correlate this with an anti-inflammatory effect of glyburide on the immune system.

Journal Article.  4718 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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