Clearance of [125I] tumor necrosis factor-α from the brain into the blood after intracerebroventricular injection in rats

To test the hypothesis that brain to blood clearance is a mechanism by which brain inflammation and damage can increase circulating acute phase cytokines, rate of transfer of [I-125]-tumor necrosis factor-alpha ([I-125]-TNF) from brain to blood was determined. Acid precipitable [I-125]-TNF appeared in peripheral brood within 5 min of intracerebroventricular (i.c.v.) injection and was cleared from brain to blood following first order kinetics at a fractional rate of 0.01123 +/- 0.0030/min, a value virtually identical with a previously determined clearance rate of [I-125]-IL-6. Area under blood concentration curve compared with that after intravenous injection shows that 31.6 +/- 5.8% of the intracerebral dose reached peripheral blood in 4 h. Elevated ratios of superior sagittal sinus to aortic blood radioactivity concentration at 1 and 3 h (1.48 +/- 0.26, p = 0.042; 1.95 +/- 0.39, p = 0.026, respectively) indicate that TNF-a drains from brain at least in part via the sagittal sinus. Escherichia coli lipopolysaccharide i.c.v. injection increased the rate of brain efflux of TNF-alpha.