The relation of pyrexia and nasal inflammatory response to virus levels in nasal washings of ferrets infected with influenza viruses of differing virulence.

Virus titres in the nasal washes of ferrets infected with recombinant influenza virus A/PR/8/34-A/England/939/69 (H3N2) clones 7a (virulent) and 64d (attenuated) showed four phases; a phase of logarithmic increase, a plateau, a period of rapid decline and a small rise on the 4th day. The virulent clone remained in the phase of logarithmic increase longer, reached plateau levels 10-fold higher and took longer to reduce to low levels than the attenuated clone. Pyrexia (more severe and prolonged for clone 7a) and inflammatory response (similar for both clones, consisting of 90% polymorphonuclear (PMN) and 10% mononuclear (MN) phagocytes) occurred at about the same time (25-29 h after inoculation) for both clones. However, the onset of the period of rapid decline of clone 64d in the nasal washes occurred 4-8 h before that for 7a in 11 of 16 ferrets. Furthermore, significant correlations were found between increases in temperature and numbers of inflammatory cells and subsequent reductions in virus titres in nasal washes; and the delay between the responses and subsequent correlated reductions of virus was less for clone 64d than for clone 7a. Thus, a link between temperature rise and inflammatory response and subsequent reduction of virus titre was detected and, whatever the mechanisms of this link, it acted differentially on the clones of differing virulence. However, the period of logarithmic increase of clone 64d ended before pyrexia and inflammation were detected and, in the plateau stage at the onset of the host responses, there were no significant correlations between them and virus levels measured at the same time or shortly afterwards. Pyrexia and inflammation also seemed to be connected with decline of virus recoveries for infections with virus strains A/PR/8/34 (HoN1) and A/New Jersey/18/76 (Hsw15N1). The significance of the relations between pyrexia and cell response and decline of virus titres in nasal washings is discussed.