The levels of interleukin (IL)-1 beta, IL-6, tumour necrosis factor (T
NF)-alpha, and macrophage inflammatory protein (MIP)-1 alpha released
from human peripheral blood leucocytes (PBL) following interaction wit
h 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 interfero
n (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 fev
ers 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 inducti
on of known pyrogenic cytokines is responsible for the febrile respons
e in influenza. The possibility that some other mediator(s) may be inv
olved cannot be ruled out. (C) 1997 Wiley-Liss, Inc.