Cytokines and the acute phase response to influenza virus in mice

Am J Physiol. 1995 Jan;268(1 Pt 2):R78-84. doi: 10.1152/ajpregu.1995.268.1.R78.


This study characterized selected aspects of the acute phase response after intranasal inoculation of mice with two doses of mouse-adapted influenza virus differing in lethality. Mice given 140 plaque-forming units (PFU) of virus (58% survival) gradually decreased food and water intake to nearly zero over 6 days; survivors then slowly increased intakes. Declines in these behaviors were parallel to decreases in body temperature and general locomotor activity and were associated with elevated activities of interleukin-6 (IL-6), tumor necrosis factor-alpha, and interferons in lung lavage fluid. Circulating levels of these cytokines 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 cytokine activities in the lungs are elevated in a time frame that supports the hypothesis that cytokines could mediate behavioral and physiological changes in mice during acute influenza infections.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Body Temperature
  • Body Weight
  • Bronchoalveolar Lavage Fluid
  • Cytokines / blood
  • Cytokines / metabolism*
  • Drinking Behavior
  • Feeding Behavior
  • Influenza A virus*
  • Interferons / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Motor Activity
  • Orthomyxoviridae Infections / blood
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / physiopathology*
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interferons