Effects of ovariectomy on the inflammatory responses of female rats to the central injection of lipopolysaccharide

Highlight
- Ovariectomized (OVX) rats show increased response to systemic LPS injection.
- The changes of inflammatory responses to central LPS injection in OVX rats were evaluated.
- OVX rats showed increased hypothalamic inflammatory responses to central LPS injection.
- Supplementation of estradiol could not attenuate the inflammatory responses in OVX rats.
- OVX increases the hypothalamic sensitivities to LPS independent of the estradiol deficiency.

It has been reported that obesity leads to more marked inflammatory responses in a site-specific manner. As has been seen in other animal models of obesity, ovariectomized rodents exhibit obesity and exacerbated fever and anorectic responses to the systemic injection of lipopolysaccharide (LPS). Furthermore, they also display increased pro-inflammatory cytokine expression in several central and peripheral tissues. Interestingly, the alterations observed in the hypothalamus are more marked than those seen in other peripheral tissues. In this study, the effects of ovariectomy on hypothalamic inflammatory responses were evaluated using the central LPS injection method. LPS was intracerebroventricularly (i.c.v.) injected into ovariectomized and gonadally intact female rats, and the immune responses of the two groups were compared. The ovariectomized rats exhibited heavier body weights than the gonadally intact rats. In addition, the ovariectomized rats displayed stronger febrile responses than the gonadally intact rats. After the i.c.v. injection of LPS, the hypothalamic interleukin (IL)-1β, IL-6, and cyclooxygenase 2 mRNA levels of the ovariectomized rats were significantly higher than those of the gonadally intact rats. The effects of estradiol supplementation on the rats' immune responses were also examined. However, the febrile responses and hypothalamic IL-1β, IL-6, and TNF-α mRNA levels of estradiol-supplemented ovariectomized rats and body weight matched oil-administered (control) rats did not differ after the i.c.v. injection of LPS. These results indicate that hypothalamic sensitivity to LPS is increased in ovariectomized rats and that this change is induced by the indirect effects of gonadal steroid deficiency. As is seen in other obese animal models, ovariectomy-induced obesity might play important roles in the exacerbated inflammatory responses observed in ovariectomized rats.