Premium
Nonsteroidal Anti‐Inflammatory Drugs Increase Tumor Necrosis Factor Production in the Periphery but Not in the Central Nervous System in Mice and Rats
Author(s) -
Sacco Silvano,
Agnello Davide,
Sottocorno Marcello,
Lozza Gianluca,
Monopoli Angela,
Villa Pia,
Ghezzi Pietro
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71052063.x
Subject(s) - tumor necrosis factor alpha , medicine , ibuprofen , lipopolysaccharide , central nervous system , endocrinology , prostaglandin , dexamethasone , iloprost , pharmacology , inflammation , prostaglandin e2 , prostacyclin
Nonsteroidal anti‐inflammatory drugs (NSAIDs), which inhibit prostaglandin (PG) synthesis, augment production of tumor necrosis factor (TNF) in most experimental models. We investigated the effect of two NSAIDs, indomethacin and ibuprofen, on the production of TNF in the CNS induced by intracerebroventricular injection of lipopolysaccharide (LPS). Indomethacin and ibuprofen, administered intraperitoneally, augmented (three‐ to ninefold) the levels of TNF in serum and peripheral organs of mice injected intraperitoneally with LPS and in rats with adjuvant arthritis (up to a sevenfold increase). However, NSAIDs (intraperitoneally or intracerebroventricularly) did not increase brain TNF production induced by intravenous LPS. In fact, indomethacin decreased (1.4–1.8‐fold) TNF levels in the spinal cord of rats with experimental autoimmune encephalomyelitis and in the cortex of rats with focal cerebral ischemia. Systemic administration of iloprost inhibited serum TNF levels after intraperitoneal LPS, whereas intracerebroventricular injection of iloprost or PGE 2 did not inhibit brain TNF induced by intracerebroventricular LPS. Both peripheral and central TNF productions were inhibited by cyclic AMP level‐elevating agents or dexamethasone. Thus, a PG‐driven negative feedback controls TNF production in the periphery but not in the CNS.