Inhibition of the Local Inflammatory Response in Man by Antimetabolites

Abstract

The effects of chemotherapy on the local inflammatory response in man were studied in 33 patients. Inhibition of the mononuclear cell phase of the response at 4, 8 and 24 hours was noted. The median on-therapy values at these hours were 0, 8.5 and 23 per cent compared to control values of 4, 24.5 and 86 per cent, respectively. The 24-hour values for the individual types of therapy were 13.5 per cent for intensive combination therapy with 4 antitumor agents, 21 per cent for 6-mercaptopurine given i.v. daily for 5 days, 2 per cent for methotrexate given i.v. daily for 5 days, 37 per cent for intermittent methotrexate and 56 per cent for other therapy. Recovery was substantial within 5 days of the end of therapy. The inhibition was not correlated with alterations in the levels of circulating granulocytes or lymphocytes, nor with the numbers of granulocytes entering the inflammatory site. Complicating infections were noted in eight patients, seven of whom were in the most strongly inhibited group. Observations of the response in ten untreated patients with acute leukemia showed both impaired granulocyte and mononuclear phases of the response.