Hypoxia-induced sickness behaviour.

Area of Science:

• Physiology
• Immunology
• Neuroscience

Background:

• Sickness behavior (SB) encompasses adaptive host responses to infection and inflammation, including fever, lethargy, and hypophagia.
• Immune mediators like cytokines and prostaglandins are thought to induce SB by acting on the central nervous system.
• Severe infections can cause hypoxia, impairing gas exchange in vital organs.

Purpose of the Study:

• To investigate the hypothesis that hypoxia can provoke sickness behavior.
• To elucidate the role of Interleukin-6 (IL-6) and prostaglandin pathways in hypoxia-induced SB.

Main Methods:

• Mice were exposed to hypoxia (11% O(2)) for 7 days.
• Interleukin-6 deficient (IL-6 KO) mice were used to assess IL-6's role.
• Pharmacological agents, mepacrine (phospholipase A(2) blocker) and indomethacin (cyclooxygenase inhibitor), were used to study recovery mechanisms.
• Plasma IL-6 and blood prostaglandin E(2) (PGE(2)) levels were measured.

Main Results:

• Hypoxia exposure induced all observed symptoms of sickness behavior in mice.
• IL-6 deficient mice exhibited reduced SB symptoms under hypoxic conditions.
• Recovery from hypoxia was not affected by mepacrine but was significantly impaired by indomethacin.
• Hypoxemia elevated plasma IL-6 levels but inhibited blood PGE(2) generation.

Conclusions:

• Hypoxia is a potent trigger of sickness behavior.
• IL-6 contributes significantly to the development of hypoxia-induced SB.
• The accumulation of free arachidonic acid in biomembranes, influenced by IL-6, plays a role in hypoxemia-induced SB, with prostaglandin synthesis being differentially affected.