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Inhibition of Hemagglutinin Synthesis by Cytoxan¹

( Department of Microbiology, University of Oregon Medical School, Portland, Oregon)

Inhibition of hemagglutinin synthesis by Cytoxan, an alkylating agent of the cyclophosphamide group, was studied in Swiss mice. The procedure involved immunization with human and with sheep erythrocytes and the determination of hemagglutinin titers of individual mice at various intervals after immunization. The minimal suppressive dose of Cytoxan was 80 mg/kg 4 hr after and 60 mg/kg 24 hr after antigen administration. Pretreatment with 200 mg/kg, but not with 100 and 60 mg/kg, was inhibitory. The most sensitive period was 24–48 hr after antigen coinciding with the induction phase. The productive phase of antibody synthesis was unusually susceptible in that depression of the primary response was obtained with single doses of Cytoxan given up to 15, but not 18 and 21, days after antigenic stimulation. The secondary response was suppressed by 200 mg/kg of Cytoxan given from 24 hr before to 72 hr after antigen. Cytoxan-resistant cells did not appear with single minimal doses given 24 hr after primary, secondary and tertiary antigenic stimuli in the same mice. The data are compared with those previously obtained with purine analogs.

¹ This work has been supported by grant A1-2661-05 from the National Institutes of Allergy and Infectious Diseases, NIH, USPHS.

Received 7/30/64. Revised 1/19/65.

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