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Cytokines and the acute phase response to influenza virus in mice
C A Conn1, J L McClellan, H F Maassab
1Institute for Basic and Applied Medical Research, Lovelace Institutes, Albuquerque, New Mexico 87108.
Abstract:
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.
Insights
Influenza infection in mice causes decreased food intake, body temperature, and activity. Elevated lung cytokines, like interleukin-6, correlate with these sickness behaviors during acute influenza.
Area of Science:
- Immunology
- Virology
- Neuroscience
Background:
- The acute phase response involves physiological and behavioral changes during infection.
- Cytokines play a role in mediating sickness behaviors.
Purpose of the Study:
- To investigate the relationship between influenza virus dose, acute phase response, and cytokine activity in mice.
- To determine if local lung cytokine levels correlate with behavioral and physiological changes.
Main Methods:
- Mice were intranasally inoculated with two different doses of mouse-adapted influenza virus.
- Food and water intake, body temperature, and locomotor activity were monitored.
- Cytokine levels (IL-1, IL-6, TNF-alpha, interferons) were measured in lung lavage fluid.
Main Results:
- Lower virus dose (140 PFU) led to gradual declines in intake, temperature, and activity, with elevated IL-6, TNF-alpha, and interferons in lung lavage fluid.
- Higher virus dose (55,000 PFU) caused rapid decreases in intake, temperature, and activity, with elevated IL-1 and IL-6 in lung lavage fluid.
- Circulating cytokine levels did not significantly increase, suggesting localized effects.
Conclusions:
- Elevated cytokine activity in the lungs during influenza infection correlates with sickness behaviors.
- Local lung cytokine responses may mediate behavioral and physiological changes associated with influenza.
- This study supports the hypothesis that cytokines are key mediators of the acute phase response in influenza.