Chronic administration of tianeptine balances lipopolysaccharide-induced expression of cytokines in the spleen and hypothalamus of rats.
The antidepressant tianeptine has been shown to protect the hippocampus against the deleterious consequences of stress and to attenuate the behavioral and neuroendocrine effects of the cytokine inducer lipopolysaccharide (LPS). Since sickness symptoms are linked to peripheral and brain production of cytokines and pro-inflammatory cytokines can promote neurotoxicity, the present study was undertaken to test the possibility that tianeptine attenuates production of pro-inflammatory cytokines. This hypothesis has been tested by studying the effects of a chronic intraperitoneal (i.p.) administration of tianeptine (10 mg/kg twice a day for 21 days) to rats on the induction by LPS (250 microg/kg, i.p.) of the production of pro- and anti-inflammatory cytokines, at the periphery (spleen, pituitary) and in the brain (hypothalamus, hippocampus). The expression of mRNAs coding for IL-1 beta, TNF-alpha, IL-6 or IL-10 (RT-PCR) and plasma levels of IL-1 beta, TNF-alpha and IL-10 (ELISA) were measured at various time intervals following LPS. Chronic tianeptine treatment attenuated LPS-induced expression of TNF-alpha in the spleen as well as plasma levels of this cytokine and altered the central balance between pro- and anti-inflammatory cytokines (IL-1 beta/IL-10). These results open new vistas in the pharmacological activity of tianeptine and provide further insights on the possible mechanisms of action involved in its neuroprotective properties.
Castanon
Nathalie
N
INRA-INSERM U394; Neurobiologie Intégrative, Institut François Magendie, Rue Camille Saint-Saëns, 33077 Bordeaux cedex, France.
Médina
Chantal
C
Mormède
Cécile
C
Dantzer
Robert
R
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects* / Q000378:metabolism; D013841:Thiazepines / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000929:Antidepressive Agents, Tricyclic; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D013841:Thiazepines; D014409:Tumor Necrosis Factor-alpha; C050504:tianeptine; D016753:Interleukin-10