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 component of many diseases. In this study the ability of commonly used antibiotics to inhibit an in vitro model of granuloma formation were studied. The effect of protein kinase C inhibition in this system was also investigated.

RESULTS

Ampicillin, cephalothin, metronidazole, rifampin, isoniazide, erythromycin, and clindamycin were inactive in inhibiting granuloma formation. Tetracycline, doxycycline, minocycline, and ciprofloxacin produced dose-dependent inhibition of the granuloma model in concentrations between 10(-4) and 10(-6) mol/L. The approximate order of descending potency was doxycycline equals minocycline greater than tetracycline greater than ciprofloxacin. The same drugs were tested for the ability to inhibit protein kinase C. Drugs inactive in the granuloma model had no effect on protein kinase C activity. The tetracyclines and ciprofloxacin all caused a dose-dependent inhibition of protein kinase C activity in the same order of relative potency as was found for inhibition of granuloma formation.

CONCLUSIONS

These data demonstrate a previously unappreciated activity of the tetracyclines and ciprofloxacin. Inhibition of granuloma formation helps to account for the activity of these drugs in the severest forms of inflammatory acne.