INHIBITION OF A MODEL OF IN-VITRO GRANULOMA-FORMATION BY TETRACYCLINES AND CIPROFLOXACIN - INVOLVEMENT OF PROTEIN-KINASE-C

Background and Design: Granulomatous inflammation is a common componen t of many diseases. In this study the ability of commonly used antibio tics to inhibit an in vitro model of granuloma formation were studied. The effect of protein kinase C inhibition in this system was also inv estigated. Results: Ampicillin, cephalothin, metronidazole, rifampin, isoniazide, erythromycin, and clindamycin were inactive in inhibiting granuloma formation. Tetracycline, doxycycline, minocycline, and cipro floxacin produced dose-dependent inhibition of the granuloma model in concentrations between 10(-4) and 10(-6) mol/L. The approximate order of decending potency was doxycycline equals minocycline greater than t etracycline greater than ciprofloxacin. The same drugs were tested for the ability to inhibit protein kinase C. Drugs inactive in the granul oma model had no effect on protein kinase C activity. The tetracycline s and ciprofloxacin all caused a dose-dependent inhibition of protein kinase C activity in the same order of relative potency as was found f or inhibition of granuloma formation. Conclusions: These data demonstr ate a previously unappreciated activity of the tetracyclines and cipro floxacin. Inhibition of granuloma formation helps to account for the a ctivity of these drugs in the severest forms of inflammatory acne.