The Journal of antimicrobial chemotherapy · 2005
Differential effects of beta-lactams on human IFN-gamma activity.
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Brooks Bernadette M, Hart C Anthony, Coleman John W
Аннотация
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.
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.