Dual effect of central injection of recombinant rat interleukin-4 on lipopolysaccharide-induced sickness behavior in rats

Neuropsychopharmacology. 2002 Jan;26(1):86-93. doi: 10.1016/S0893-133X(01)00305-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Exploratory Behavior / drug effects
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Interleukin-4 / administration & dosage
  • Interleukin-4 / pharmacology*
  • Interleukin-4 / toxicity*
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / antagonists & inhibitors*
  • Lipopolysaccharides / toxicity*
  • Male
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Social Behavior
  • Time Factors


  • Lipopolysaccharides
  • Recombinant Proteins
  • Interleukin-4