Inhibition of Cigarette Smoke-Induced Airway Secretory Cell Hyperplasia by Indomethacin, Dexamethasone, Prednisolone, or Hydrocortisone in the Rat

Abstract

As the nonsteroidal anti-inflammatory drug indomethacin has already been shown to inhibit cigarette smoke (CS)-induced secretory cell hyperplasia in the airway epithelium of the rat, the present study was undertaken to determine the effects of prophylactic interaperitoneal injection of indomethacin (4 mg/kg body weight) compared with each of three steroidal anti-inflammatory drugs given at comparable doses. The results show that dexamethasone (given initially at 4 mg/kg), prednisolone (4 mg/kg) and hydrocortisone (4 mg/kg) were also inhibitory. Dexamethasone proved to be toxic and its dose had to be reduced to give an average dose of 2 mg/kg over the experimental period. Prednisolone and hydrocortisone were toxic only when in combination with CS. The order of descending effectiveness in inhibiting secretory cell hyperplasia was indomethacin, dexamethasone, prednisolone and hydrocortisone. Indomethacin was the most effective drug in the trachea, whilst in distal intra-pul-monary airways dexamethasone was the most effective. Depending on airway level, inhibition was between 69 and 115% of the value obtained after CS alone. The inhibition was complete in all but one instance. The results show that steroids also inhibit secretory cell hyperplasia but at a comparable dose they are generally less effective than indomethacin and may have unacceptable side effects.