Centrally administered interleukin (IL)-1 [both α and β forms, 200 ng/rat intracerebroventricularly (icv)] results in a larger increase in serum IL-6 than after systemic injection, indicating the brain's role in the acute phase response. This action was prevented by the IL-1-receptor antagonist IL- 1Ra (20 μg/rat icv). Neither antiserum against corticotropin-releasing factor (CRF) nor the α-helical-CRF antagonist (25 μg/rat icv) affected IL- 6 induction by central IL-1β, which, however, was significantly prevented by the synthetic glucocorticoid dexamethasone [3 mg/kg intraperitoneally (ip)]. Naloxone, the opiate antagonist, but not naloxone methiodide, its quaternary salt that does not penetrate the blood-brain barrier (both administered at 10 mg/kg ip), antagonized this action of IL-1β. After intracerebroventricular IL-1β, IL-6 levels in brain areas (striatum, hippocampus, hypothalamus) were extremely low, suggesting that the brain does not significantly contribute to IL-6 synthesis in this condition. The results show that induction of high serum IL-6 levels by central IL-1β is mediated by brain IL-1 receptors and is sensitive to inhibition by corticosteroids. The inhibitory effect of naloxone suggests that central opiates are required for this action of IL- 1β.
|Journal||American Journal of Physiology - Regulatory Integrative and Comparative Physiology|
|Issue number||4 34-4|
|Publication status||Published - 1993|
- corticotropin- releasing factor
- interleukin-1-receptor antagonist
ASJC Scopus subject areas