Interleukin-1 beta enhances spinal cord blood flow after intrathecal administration in the normal rat.
The effects of acute intrathecal recombinant human interleukin-1 beta (rhIL-1 beta) administration on spinal cord blood flow (SCBF), volume, and velocity were determined by laser-Doppler flowmetry in normal anesthetized rats with the use of a randomized and blinded protocol. The intrathecal administration of rhIL-1 beta (0.16-16 ng) produced a dose-dependent increase in SCBF that was not related to changes in blood pressure; arterial pH, PO2, PCO2; or spinal cord temperature. The IL-1 beta-induced enhancement of SCBF was directly proportional to the resultant elevation of spinal cord rhIL-1 beta content and was significantly correlated with an elevated blood velocity. The IL-1 receptor antagonist (IL-1ra) in concentrations 50- and 200-fold higher than IL-1 beta completely blocked the IL-1 beta-induced increase in SCBF when both compounds were administered concomitantly, but when administered alone, IL-1ra did not affect SCBF or other parameters. This suggests that IL-1 beta action was mediated by a specific interaction with an IL-1 membrane receptor site. The results suggest a role of IL-1 beta in the regulation of spinal cord hemodynamics. A potential pharmacological approach using IL-1 agonists for the treatment of the delayed appearance of posttraumatic spinal ischemia is proposed.
Plata-Salamán
C R
CR
Alfred I. duPont Institute, Wilmington 19899, USA.
Kelly
G
G
Agresta
C
C
Taylor
K
K
Salzman
S K
SK
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007278:Injections, Spinal; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012007:Rectum; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply* / Q000502:physiology
D007375:Interleukin-1; D011994:Recombinant Proteins