Differential effects of β-lactams on human IFN-γ activity

Abstract

Objectives: To investigate whether a range of β-lactam antibiotics conjugate to and hence reduce the activity of IFN-γ, as has been shown for penicillin G. A selection of penicillins, cephalosporins, a monobactam (aztreonam), a β-lactamase inhibitor (clavulanic acid), a carbapenem (meropenem) and the non-β-lactam penicillin derivative D-penicillamine were tested for their effect on IFN-γ activity. Methods: Following exposure to a range of concentrations of these compounds, for varying lengths of time, IFN-γ 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-γ 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-γ activity. Conclusions: β-Lactams differ in their capacity to modulate human IFN-γ activity. This finding may have implications for the immunomodulatory effects of β-lactams and for the design both of β-lactams that do not affect the immune system and those which may be used therapeutically to target cytokine action. © The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.