We demonstrated in a previous study that serum interleukin (IL)-8 concentrations were significantly higher in women with hot flashes than without hot flashes. To clarify the role of IL-8 in the pathoetiology of menopausal hot flashes, we examined the effect of rat cytokine-induced neutrophil chemoattractant (CINC), a member of the IL-8 family, on thermoregulation using ovariectomized (OVX) rats treated with intracerebroventricular (i.c.v.) injection of luteinizing hormone-releasing hormone agonist (LH-RHa) as a model of hot flashes.

We found that 1) expression of CINC mRNA was increased around the periventricular area in the hypothalamus at 1 hour and the serum CINC concentration was increased at 2 hours after i.c.v. injection of LH-RHa, 2) the increase in serum CINC concentration in hypophysectomized rats was significantly lower than that in sham-operated rats, 3) i.c.v. but not intravenous injection of CINC elevated the rectal temperature of OVX rats, 4) i.c.v. injection of LH-RHa into OVX rats produced a rapid rise (maximal increase: 10–25 min) in tail skin temperature, and the elevation was augmented by injection of an anti-CINC antibody, and 5) changes in serum CINC concentration and skin temperature following i.c.v. injection of LH-RHa were reversed by replacement of estradiol.

In conclusion, the production of CINC in the hypothalamus due to LH-RHa injection in OVX rats was increased after elevation of skin temperature, suggesting that CINC plays a key role in the homeostasis of body temperature. Disturbance of the thermoregulatory mechanism involving LH-RH and CINC may be related to the pathoethiology of hot flashes.