Interleukin-1 stimulates the central release of corticotropin-releasing hormone in the primate

The cytokine interleukin-1 (IL-1) is present in the brain and is known to cause a variety of neuroendocrine and immune effects in the rodent; the neuropeptide corticotropin-releasing hormone (CRH) plays a critical role in mediating many of these effects. Little is known about these neuropeptide interactions in the primate. We have therefore examined the effects of IL-1 alpha on the release of CRH in the ovariectomized rhesus monkey in vitro and in vivo. In 3 animals, the effect of IL-1 alpha on CRH release from the superfused hypothalamus was studied in vitro. The hypothalamus was divided in half and fragments from each half were superfused separately. Mean CRH release was 262 +/- (SE) 46 pg/20 min and increased to 1,340 +/- 470 pg/20 min after exposure to IL-1 alpha (p < 0.05). The effect of IL-1 alpha on CRH release into cerebrospinal fluid (CSF) in vivo was studied in 8 animals with chronic cannulas implanted in the lateral ventricle for IL-1 infusion; indwelling catheters were also placed via lumbar puncture and threaded into the cervical area for CSF collection. CSF was collected at a rate of 800 microliters/h during a 4-hour baseline period and for 4-8 h after intracerebroventricular infusion of 4.2 micrograms of IL-1 alpha. CRH increased significantly over time in CSF after IL-1 alpha infusion; the mean concentration of CRH increased from 83 +/- 17 pg/ml during the baseline period to 203 +/- 40 pg/ml after IL-1 alpha infusion (p < 0.01). We conclude that IL-1 stimulates central CRH release in the primate and that the effects of cytokines on the release of this important neuromodulator can be monitored in chronically cannulated animals in vivo.