Dual effect of central injection of recombinant rat interleukin-4 on lipopolysaccharide-induced sickness behavior in rats.
Systemic administration of the bacterial endotoxin lipopolysaccharide (LPS) has profound depressive effects on behavior that are mediated by the inducible expression of pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-6 and tumor necrosis factor alpha (TNF), in the brain. To assess the regulatory effects of the anti-inflammatory cytokine IL-4 on LPS-induced sickness behavior, rats injected intra-peritoneally (i.p.) with LPS were administered intracerebroventricularly (i.c.v.) with IL-4. IL-4 (30 and 300 ng) potentiated the behavioral effects of LPS (175 microg/1000 g) when both molecules were co-injected. However, when IL-4 (30 ng) was injected 12 h prior to LPS, it blocked the depressing effects of LPS on social exploration. These results indicate that the regulation of cytokine-induced sickness behavior by IL-4 can be either inhibitory or stimulatory depending on the sequencing of IL-4 and LPS treatments.
Bluthé
Rose Marie
RM
Integrative Neurobiology Laboratory, INRA-INSERM U394, Institut François Magendie, Rue Camille Saint-Saëns, 33077, Bordeaux cedex, France. rose-marie.bluthe@bordeaux.inserm.fr
Lestage
Jacques
J
Rees
Gwen
G
Bristow
Adrian
A
Dantzer
Robert
R
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D015847:Interleukin-4 / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012919:Social Behavior; D013997:Time Factors
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D015847:Interleukin-4