IN-VIVO SYNTHESIS OF TUMOR-NECROSIS-FACTOR-ALPHA IN HEALTHY HUMANS AFTER LIVE YELLOW-FEVER VACCINATION

Most knowledge about the synthesis of human tumor necrosis factor (TNF )-alpha and its regulation derives from in vitro studies. The hypothes is that the syndrome of malaise, myalgia, and low fever observed after a vaccination with live attenuated yellow fever virus could be associ ated with increased synthesis of TNF was investigated. Plasma samples of 15 healthy subjects taken before and until day 2 (until day 11 in 5 of these subjects) after yellow-fever vaccination, showed a significa nt increase of plasma TNF concentration on day 2 after vaccination and a second peak on day 7. Interleukin-1 receptor antagonist (IL-1ra) co ncentration was significantly elevated in all subjects on day 2 after vaccination. In a control group receiving non-live vaccinations, TNF a nd IL-1ra concentrations were unchanged. Thus, yellow fever vaccinatio n represents a routine medical intervention that results in a reproduc ible increase in the plasma concentration of TNF and secondary cytokin es. This may serve as a unique model for the study of the regulation o f TNF synthesis in vivo.