Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammation causes the induction of cyclooxygenase-2 (Cox-2), leading to the release of prostanoids, which sensitize peripheral nociceptor terminals and produce localized pain hypersensitivity. Peripheral inflammation also generates pain hypersensitivity in neighbouring uninjured tissue (secondary hyperalgesia), because of increased neuronal excitability in the spinal cord (central sensitization), and a syndrome comprising diffuse muscle and joint pain, fever, lethargy and anorexia. Here we show that Cox-2 may be involved in these central nervous system (CNS) responses, by finding a widespread induction of Cox-2 expression in spinal cord neurons and in other regions of the CNS, elevating prostaglandin E2 (PGE2) levels in the cerebrospinal fluid. The major inducer of central Cox-2 upregulation is interleukin-1beta in the CNS, and as basal phospholipase A2 activity in the CNS does not change with peripheral inflammation, Cox-2 levels must regulate central prostanoid production. Intraspinal administration of an interleukin-converting enzyme or Cox-2 inhibitor decreases inflammation-induced central PGE2 levels and mechanical hyperalgesia. Thus, preventing central prostanoid production by inhibiting the interleukin-1beta-mediated induction of Cox-2 in neurons or by inhibiting central Cox-2 activity reduces centrally generated inflammatory pain hypersensitivity.
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PMID:Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. 1126 Jun 97

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.
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PMID:Hypoxia-induced sickness behaviour. 1724 71