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JAC Advance Access originally published online on October 20, 2005
Journal of Antimicrobial Chemotherapy 2005 56(6):1122-1125; doi:10.1093/jac/dki373
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Differential effects of ß-lactams on human IFN-{gamma} activity

Bernadette M. Brooks1,*, C. Anthony Hart2 and John W. Coleman1

1 Department of Pharmacology and Therapeutics, University of Liverpool, Ashton Street, Liverpool L69 3GE, UK; 2 Department of Medical Microbiology and G U Medicine, University of Liverpool, Liverpool, UK

Received 3 December 2004; returned 8 March 2005; revised 19 September 2005; accepted 20 September 2005

* Corresponding author. Tel: +44-151-794-5543; E-mail: spjbmb{at}btinternet.com

Objectives: To investigate whether a range of ß-lactam antibiotics conjugate to and hence reduce the activity of IFN-{gamma}, as has been shown for penicillin G. A selection of penicillins, cephalosporins, a monobactam (aztreonam), a ß-lactamase inhibitor (clavulanic acid), a carbapenem (meropenem) and the non-ß-lactam penicillin derivative D-penicillamine were tested for their effect on IFN-{gamma} activity.

Methods: Following exposure to a range of concentrations of these compounds, for varying lengths of time, IFN-{gamma} activity was assayed by induction of CD54 on the surface of the lung epithelial cell line A549, utilizing an ELISA.

Results: Clavulanic acid, cefoxitin and cefaloridine were the most potent inhibitors of IFN-{gamma} activity, followed by cefotaxime, ceftriaxone and phenoxymethylpenicillin. Ampicillin was less inhibitory than penicillin G, whilst meropenem and aztreonam had the least effect and D-penicillamine had no effect. The modulatory effect of these compounds was not due to a direct effect on CD54 induction. Unlike freshly prepared drugs, aged preparations of penicillin G and clavulanic acid had no significant effect on IFN-{gamma} activity.

Conclusions: ß-Lactams differ in their capacity to modulate human IFN-{gamma} activity. This finding may have implications for the immunomodulatory effects of ß-lactams and for the design both of ß-lactams that do not affect the immune system and those which may be used therapeutically to target cytokine action.

Keywords: cytokines , immunomodulation , drugs , modulation , interactions


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