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JAC Advance Access published online on October 20, 2005
Journal of Antimicrobial Chemotherapy, 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
Received December 3, 2004
Revised September 19, 2005
Accepted September 20, 2005

Brief report

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

Bernadette M. Brooks 1*, C. Anthony Hart 2, and John W. Coleman 1

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

* To whom correspondence should be addressed.
Bernadette M. Brooks, E-mail: spjbmb{at}btinternet.com


  Abstract

Objectives: To investigate whether a range of {beta}-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 {beta}-lactamase inhibitor (clavulanic acid), a carbapenem (meropenem) and the non-{beta}-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: {beta}-Lactams differ in their capacity to modulate human IFN-{gamma} activity. This finding may have implications for the immunomodulatory effects of {beta}-lactams and for the design both of {beta}-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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