Effects of different cyclophosphamide treatment schedules on collagen and collagenolytic activity in granulation tissue.

Cyclophosphamide was injected intraperitoneally into rats in doses of 6 or 10 mg/kg/day. The controls had daily intraperitoneal injections of physiological saline. After 14 days of treatment, granulation tissue was produced by subcutaneous implantation of viscose cellulose sponges. The treatment with cyclophosphamide and physiological saline was continued in different sequences for a further one or two 14-day periods. The rats were killed 14 or 28 days after the sponge implantation. Cyclophosphamide caused a decrease in body weight, in the number of leucocytes, in granuloma dry weight and in the granuloma content of free OH-proline while the water percentage increased. Ten mg/kg/day of cyclophosphamide had a more pronounced effect than 6 mg/kg/day. The results are consistent with an inhibitory effect of cyclophosphamide on granuloma formation and on the degradation of collagen. Accordingly, measurements of collagenolytic activity in granulation tissue after culture in vitro suggested an inhibition of collagenolysis after cyclophosphamide treatment. No effect of pretreatment was observed, and the effect of cyclophosphamide was independent of whether cyclophosphamide was given during the early or late phase of granulation tissue production.