CYTOKINES AND THE ACUTE-PHASE RESPONSE TO INFLUENZA-VIRUS IN MICE

This study characterized selected aspects of the acute phase response after intranasal inoculation of mice with two doses of mouse-adapted i nfluenza virus differing in lethality. Mice given 140 plaque-forming u nits (PFU) of virus (58% survival) gradually decreased food and water intake to nearly zero over 6 days; survivors then slowly increased int akes. Declines in these behaviors were parallel to decreases in body t emperature and general locomotor activity and were associated with ele vated activities of interleukin-6 (IL-6), tumor necrosis factor-alpha, and interferons in lung lavage fluid. Circulating levels of these cyt okines were not increased. After 55,000 PFU of virus (100% mortality), food and water intake fell to near zero within 48 h, temperature and locomotor activity decreased significantly, and activities of IL-1 and IL-6 were elevated in lung lavage fluid. These data show that cytokin e activities in the lungs are elevated in a time frame that supports t he hypothesis that cytokines could mediate behavioral and physiologica l changes in mice during acute influenza infections.