Recovery of humoral and cellular immunity by soluble mediators after 5-fluorouracil-induced immunosuppression.
5-Fluorouracil (5-FU) administered in daily injections to mice (15-60 mg/kg; subcutaneous) was differentially toxic to helper T cells. Precursors for both antibody forming cells and cytotoxic T lymphocytes (CTL) were spared. 5-FU suppressed the in vitro T cell-dependent antibody response to sheep red blood cells (SRBC). This low response was restored to normal levels by the addition of T cell replacing factor (TRF) or mixed lymphocyte culture (MLC) supernatants to the culture system. T cell-independent antibody responses to TNP-Ficoll or TNP-LPS were not eliminated by 5-FU but, in contrast, were elevated two-four-fold. These results indicate that precursors for antibody forming cells for T cell-dependent and -independent antibody responses were not eliminated by 5-FU, 5-FU administered in the same regimen did not reduce the number of CTL precursors as shown by limiting dilution analysis, but did cause a reduction in the capacity of lymphocytes from pre-treated mice to generate a CTL response in vitro. This low CTL response was restored to control levels by adding Lyt 1+2- T cells or sources of interleukin 2 (IL2) to the culture system, indicating that 5-FU similarly eliminated helper cells for CTL precursor differentiation as well as helper cells for antibody synthesis.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000921:Antibody-Producing Cells / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D006462:Hemolytic Plaque Technique; D007111:Immunity, Cellular / Q000187:drug effects*; D007166:Immunosuppressive Agents; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D007166:Immunosuppressive Agents; D005472:Fluorouracil