The modification of macrophage activity in experimental granulomas by cyclophosphamide

Round glass coverslips were implanted in the subcutaneous tissue of mice previously immunized to sheep red cells (SRBC) and the same antigen injected into the pocket where the coverslip lay. It was shown that when mice received a prior dose of cyclophosphamide (Cy) the number of macrophages adherent to the glass increased, they showed more pre-mitotic DNA synthesis and were more phagocytic via their Fc and C3b surface receptors. However, when BCG was inoculated into similar coverslips pockets in mice not previously sensitized to BCG but pre-treated with Cy, the number of macrophages on the glass surface fell and their phagocytic potential decreased compared with non-Cy-treated controls. When BCG was inoculated into the peritoneal cavity of mice, Cy treatment induced a significant increase in the number of lesions in the peritoneal cavity compared with non-Cy treated controls. When BCG was injected into the footpad of mice it was clear that pre-treatment with Cy abolished the increase in foot volume otherwise seen at 24 hr but led to a sustained increase in volume which reached a peak on day 6. However, when Cy was given to the mice 5 days after BCG injection the course of the response was not altered. It is concluded that treatment with Cy before an inflammatory stimulus with an immunological component, modifies macrophage function and granuloma development. Differential effects of Cy on various components of the immune response are thought to be its most likely explanation.