Are known pyrogenic cytokines responsible for fever in influenza?

The levels of interleukin (IL)-1 beta, IL-6, tumour necrosis factor (TNF)-alpha, and macrophage inflammatory protein (MIP)-1 alpha released from human peripheral blood leucocytes (PBL) following interaction with influenza virus clone 7a (virulent, produces high fever in ferrets) and A/Fiji (attenuated, produces relatively low fever in ferrets) were low and similar for the two viruses. Neither strain induced interferon (IFN)-gamma and release of IL-8 (which occurs on incubation of PBLs alone) was reduced after interaction with the two viruses. The levels of IL-1 and IL-6 detected in the plasma of infected ferrets were low and did not correlate with the onset, duration or magnitude of the fevers produced by clone 7a and A/Fiji. Relatively large amounts (100,000 pg/kg) of IL-1 and TNF-alpha were needed to produce appreciable fever in rabbits, and such quantities of IL-6 were not pyrogenic. Hence, as for previous observations, no evidence could be obtained that induction of known pyrogenic cytokines is responsible for the febrile response in influenza. The possibility that some other mediator(s) may be involved cannot be ruled out.