To test the hypothesis that leptin was secreted from the brain into the blo
od of the rat, its concentration was measured in the superior sagittal sinu
s (SSS; which drains the cerebral cortex) and aortic blood of normal fastin
g male rats and rats that had been treated with iv or intracerebroventricul
ar (icv) injections of interleukin-1 beta (IL-1 beta; 100 ng), a cytokine p
reviously shown to induce peripheral leptin secretion. Plasma levels of lep
tin in SSS were slightly, but significantly, less than those in the aorta i
n control, saline-injected rats (0.99 +/- 0.07 vs. 1.19 +/- 0.10 ng/ml; n =
15; P = 0.03) and in rats injected with human IL-1 beta iv (1.56 +/- 0.12
vs. 1.92 +/- 0.15 ng/ml; n = 23; P = 0.004) or icy (1.38 +/- 0.11 vs. 1.57
+/- 0.12 ng/ml; n = 23; P = 0.008). IL-1 beta by either the iv or icy route
significantly increased leptin levels in the aorta [1.19 +/- 0.10 vs. 1.92
+/- 0.15 ng/ml (P = 0.0002) and 1.19 +/- 0.10 vs. 1.57 +/- 0.12 ng/ml (P =
0.022), respectively]. SSS levels of leptin were also raised after iv or i
cy injection (P = 0.0002 and P = 0.0053, respectively). These findings demo
nstrate a net uptake of leptin by the cerebral cortex from peripheral blood
in both normal and IL-1 beta-treated animals and show that peripheral bloo
d levels of leptin are increased by IL-1 beta whether administered icy or i
v.