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Involvement of Cytokine-Induced Neutrophil Chemoattractant in Hypothalamic Thermoregulation of Luteinizing Hormone-Releasing Hormone

Tsumura Research Laboratory (M.N., M.Y., Y.K.), Ibaraki 300-1192, Japan; and Department of Obstetrics and Gynecology (T.Y., M.I.), Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan

Address all correspondence and requests for reprints to: Masamichi Noguchi, Tsumura Research Laboratory, 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. E-mail: noguchi_masamichi{at}mail.tsumura.co.jp.

We demonstrated in a previous study that serum 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 LHRH agonist (LHRHa) 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 h, and the serum CINC concentration was increased at 2 h after i.c.v. injection of LHRHa; 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 iv injection of CINC elevated the rectal temperature of OVX rats; 4) i.c.v. injection of LHRHa 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 after i.c.v. injection of LHRHa were reversed by replacement of estradiol. In conclusion, the production of CINC in the hypothalamus due to LHRHa 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 LHRH and CINC may be related to the pathoetiology of hot flashes.