AJP - Regulatory, Integrative and Comparative Physiology, Vol 265, Issue 4 739-R742, Copyright © 1993 by American Physiological Society
Modulation of systemic interleukin-6 induction by central interleukin-1
M. G. De Simoni, A. De Luigi, L. Gemma, M. Sironi, A. Manfridi and P. Ghezzi
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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.
