Hypoxia-induced sickness behaviour.
Sickness behaviour (SB) consists of the set of adaptive responses of the host to severe infections and inflammation. It includes, among others, the thermoregulatory responses such as regulated increase (fever) and/or decrease (anapyrexia) of body temperature (T(b)), decrease of motor activity (lethargy), and loss of appetite (hypophagia) resulting in a transient loss of body weight. It is thought that SB is partially induced by the immune-derived mediators such as cytokines and prostaglandins acting on the central nervous system. It has repeatedly been shown, on the other hand, that severe infections (pneumonia, tissue septicemia) can impair processes of the gases exchange both in the lungs and in distal tissues including brain, which may lead to hypoxia of the affected organs. Therefore, we have tested the hypothesis that hypoxia may also provoke SB. The study was conducted on freely moving biotelemetered mice kept at 28 degrees C ambient and 12/12 h light/dark cycle. We demonstrate that mice exposed for 7 days to hypoxia (11%O(2)) displayed all symptoms of SB. Interleukin-6 deficient mice (IL-6 KO) revealed reduced SB symptoms under hypoxic conditions. Recovery of the hypoxia-exposed mice to a normal rhythm in T(b), motor activity and feeding was unaffected by mepacrine, a phospholipase A(2) blocker. The recovery, however, was significantly impaired by indomethacin, a cyclooxygenase inhibitor. Exposure to hypoxemia resulted in significant elevation of plasma IL-6 in both untreated and treated with lipopolysaccharide (LPS) mice. It inhibited, however, a generation of blood prostaglandins (PGE(2)) in mice. Based on these data we conclude that IL-6 and accumulation of free arachidonic acid in biomembranes contribute to hypoxemia- induced SB.
Kozak
W
W
Department of Immunology, Institute of General and Molecular Biology, Nicolaus Copernicus University, Toruń, Poland. wkozak@biol.uni.torun.pl
Wrotek
S
S
Walentynowicz
K
K
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001831:Body Temperature / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D015232:Dinoprostone / Q000097:blood / Q000502:physiology*; D004435:Eating / Q000502:physiology; D005334:Fever / Q000097:blood / Q000201:enzymology / Q000503:physiopathology; D000860:Hypoxia / Q000097:blood / Q000201:enzymology / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood / Q000172:deficiency / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D054467:Phospholipases A2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012803:Sick Role; D013047:Specific Pathogen-Free Organisms
D015850:Interleukin-6; D008070:Lipopolysaccharides; D011451:Prostaglandin-Endoperoxide Synthases; D054467:Phospholipases A2; D015232:Dinoprostone; D007213:Indomethacin