The effects of 5-fluorouracil on immunocompetent cells depend on the genotype of experimental animals used.
A detailed study was made of the effects of 5-fluorouracil (5-FU) on primary and secondary immune responses to a T-dependent antigen in mice. Subcutaneous, intraperitoneal and intravenous applications gave similar results, oral administration was less effective. The minimal effective dose was found to be 40 mg/kg. Inbred strains known to differ in terms of IgG immune responses were compared and found to respond quite differently to the drug. For example, when 5-FU was injected 24 h before or simultaneously with antigen, IgM plaque-forming cell (PFC) responses of C57BL/10 mice were not substantially affected. In contrast, responses of A/J and Balb/c mice were suppressed 50-90% under the same conditions. If injected 24 h after the antigen, 5-FU inhibited PFC responses completely in all three strains. IgM PFC recovery was fastest in the C57BL/10 strain and started on day 7. In secondary responses, IgM overstimulation was seen in C57BL/10 and Balb/c mice if 5-FU was injected once, i.e. 24 h after primary immunization. IgG PFC were completely suppressed in primary responses in all strains. In secondary responses, the decrease was influenced by the time of drug injection and by the genotype of the treated animal. Inhibition of isotype switching was greatest in low-IgG-responding C57BL/10 mice. These results demonstrate that genotypic variation can be substantial with respect to effects of 5-FU on the immune system.
Rihova
B
B
Institute of Microbiology, Czechoslovak Academy of Sciences, Prague.
Vetvicka
V
V
Kincade
P W
PW
D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D005838:Genotype; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D013045:Species Specificity
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D005472:Fluorouracil