Penicillin conjugates to interferon-gamma and reduces its activity: A novel drug-cytokine interaction

beta -Lactam antibiotics are the class of drug most frequently associated w ith IgE-mediated allergy but the mechanisms underlying this response are po orly understood. IFN-gamma is a key cytokine in immunity with regulatory ac tions on monocytes, NK cells, epithelial cells, and T and B lymphocytes. IF N-gamma promotes Th1 responses and inhibits Th2- and IgE-mediated responses . In this study we show, by Western blotting, that the prototype (beta -lac tam benzylpenicillin (BP) conjugates to human IFN-gamma but not to IL-4. Th e interaction of BP with IFN-gamma inhibited the cytokine's detection by im munoassay and impaired its activity, as assessed in three different assays: upregulation of MHC molecules on monocytes plus induction of nitric oxide synthesis and expression of monocyte chemoattractant protein-1 mRNA by epit helial cells. This is the first reported example of a direct drug-cytokine interaction and suggests a mechanism by which penicillin may disrupt IFN-ga mma -dependent immune responses and promote allergy. (C) 2001 Academic Pres s.