Modulation of systemic interleukin-6 induction by central interleukin-1.
Centrally administered interleukin (IL)-1 [both alpha and beta 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 micrograms/rat icv). Neither antiserum against corticotropin-releasing factor (CRF) nor the alpha-helical-CRF antagonist (25 micrograms/rat icv) affected IL-6 induction by central IL-1 beta, 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-1 beta. After intracerebroventricular IL-1 beta, 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-1 beta 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-1 beta.
De Simoni
M G
MG
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
De Luigi
A
A
Gemma
L
L
Sironi
M
M
Manfridi
A
A
Ghezzi
P
P
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors
D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D009270:Naloxone; D003907:Dexamethasone