G. W. Santos, A. Owens, L. Sensenbrenner
Mar 1, 1964
Citations
1
Influential Citations
81
Citations
Quality indicators
Journal
Annals of the New York Academy of Sciences
Abstract
Experiments were performed to detect any effect of the chemical agents employed on antibody production in man. These agents are commonly classed as cytotoxic. Mechlorethamine, cyclophosphamide, 6-mercaptopurine, 5fluorouracil, 5-fluoro-2'-deoxyuridine and methotrexate were chosen for study. Cyclophosphamide, 6-mercaptopurine, 5-fluorouracil, 5-fluoro-2'-deoxyuridine and methotrexate were found to eliminate or markedly impair the serologic response to a foreign antigen in humans with various neoplastic diseases. Mechlorethamine under the circumstances of these experiments did not interfere noticeably with the development of circulating antibodies against P. tularensis or Vi antigen. The patients who received mechlorethamine or no drug-treatment developed antibody titers in a fashion similar to that reported by Saslaw in normal men immunized with Pasteurella tularensis vaccine and by Landy in normal men given the Vi antigen. None of the chemical agents studied under the conditions of these experiments significantly altered existing red-blood-cell isoagglutinin titers or established (cutaneous) delayed hypersensitivity. In these experiments, no obvious relation between changes in the formed elements of the peripheral blood and suppression of immune responsiveness was detected. Inspection of the patient data in the various experimental categories with regard to their ages, medical diagnoses, extent of their diseases, survival times, serum albumin/globulin ratios, isoagglutinin titers and responsiveness to (delayedmore » hypersensitivity) skin tests does not suggest that any of these variables, singly or in combination, could be related to the altered antibody responses which are attributed to the drugs. Conclusions concerning the comparative effectiveness of these agents in suppressing immune responses must await completion of quantitative dose-response and dose-schedule studies. Similarly, sound extrapolations from animal studies to man must be based on careful quantitative scrutiny of the several variables involved in each experimental system. (auth)« less