Differential effects of beta-lactams on human IFN-gamma activity.
OBJECTIVE
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.
Brooks
Bernadette M
BM
Department of Pharmacology and Therapeutics, University of Liverpool, Ashton Street, Liverpool L69 3GE, UK. spjbmb@btinternet.com
Hart
C Anthony
CA
Coleman
John W
JW
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D019818:Clavulanic Acid / Q000494:pharmacology; D004847:Epithelial Cells / Q000737:chemistry; D006801:Humans; D007155:Immunologic Factors; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D010400:Penicillin G / Q000494:pharmacology; D013997:Time Factors; D047090:beta-Lactams / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D007155:Immunologic Factors; D047090:beta-Lactams; D018799:Intercellular Adhesion Molecule-1; D019818:Clavulanic Acid; D007371:Interferon-gamma; D010400:Penicillin G