Thesis Abstract

The effect of three antibiotics (ciprofloxacin, lincomycin and erythromycin) on the inflammatory process was studied both in vitro and in vivo. Agar-induced rat paw oedema was used as a model for acute inflammation, and the antibiotics were administered (10 mg/kg, 20 mg/kg and 40 mg/kg per orally) 1hour before injection of agar. Ciprofloxacin showed a dose-dependent inhibitory effect on the paw oedema though the maximum concentration (40 mg/kg b.w. dose) showed a deviation. The same pattern was observed for erythromycin. Lincomycin showed a dose dependent effect on the paw oedema. At the highest concentrations (40 mg/kg), lincomycin showed the highest inhibitory effect on the paw oedema. The only significant (p<0.05) differences between the effects of the antibiotics and the reference drug was observed with ciprofloxacin (20 mg/kg) and lincomycin (40 mg/kg) at the fifth hour post-administration. Thermal-induced pain was used for the analgesic activity test. The hot glass surface on which the rats were placed was able to cause pain on the rat paw. At 15 minutes, of all the doses of the various antibiotics, ciprofloxacin 200 mg/kg evoked the highest reaction latency to thermal-induced pain though it was non-significantly (p>0.05) lower than that of aspirin. Only aspirin and ciprofloxacin prolonged the reaction latency after 60 minutes. At 60 minutes, the reaction latency of the three doses of ciprofloxacin was significantly (p<0.05) higher than the reaction latency of lincomycin and erythromycin. Effect of the drugs on agar-induced migration of leukocytes into the peritoneum was also ascertained. All the antibiotics significantly (p<0.05) reduced leucocyte mobilization into the affected tissue. They all had their maximum inhibitory effects at the highest dose (40mg/kg) and these compared well with that of indomethacin. Erythromycin 40mg/kg showed thpre highest inhibitory effect on leucocyte migration. The control had the highest total leucocyte count (3666.67) and the highest percentage of neutrophils that migrated (63.67%). Effects of the drugs on phospholipase A2 activity were tested in vitro. The enzyme activity for the different concentrations of the test antibiotics and prednisolone were significantly (p<0.05) lower than that of the control. Enzyme activity increased with increasing concentration in ciprofloxacin and erythromycin while it reduced in lincomycin and prednisolone. Effect of the antibiotics was also tested on platelet aggregation. Ciprofloxacin-treated, erythromycin-treated and the normal control all followed a similar trend. They all had stepwise increases in absorbance from time 0 seconds through to time 120 seconds. The trend in lincomycin-treated groups differed from that of ciprofloxacin-treated and erythromycin-treated groups. There was a sharp decrease in the absorbance at around 30 seconds followed by a continuous increase up to 120 seconds and this was similar to what was obtained with indomethacin-treated groups. The present study showed that these antibiotics had anti-inflammatory activity, which probably depended on their ability to prevent the production of some pro-inflammatory mediators and cytokines, and implies that these agents, might exert anti-inflammatory effects alongside their antibacterial activity.

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