We assessed the time course effects of lipopolysaccaride (LPS) on food intake,
cytokines, and
hormones in rats and evaluated the relation between LPS-induced
anorexia and its possible causative factors. Food intake was reduced 2 h after LPS injection (500 microg/kg, intraperitoneally) and remained decreased for 24 h. Plasma
TNF-alpha and
IL-6 levels increased by LPS administration at 0.5 and 2 h, and at 2 and 4 h, respectively. Plasma
leptin and
glucose levels were elevated at 8 and 16 h, and
insulin levels were elevated at 2, 4, 8, and 16 h in the LPS-injected group, as compared to the counterpart controls.
IL-6 levels in the CSF were elevated at 2 and 4 h. Hypothalamic
cytokines tended to increase as early as 0.5 h after LPS injection and remained increased until 16 h. LPS-induced
anorexia was attenuated in
insulin-deficient STZ rats and was abolished by
insulin treatment. The hypothalamic expression of NPY, a target of
insulin's anorexic effect, was decreased 2 h after LPS administration, and central NPY injection (3 nM) prevented LPS-induced
anorexia. In conclusion,
cytokines,
insulin, and
leptin levels evidence different time courses by LPS administration. In LPS-induced
anorexia,
insulin may constitute a newly found causative factor, whereas
leptin appears to be uninvolved in an early period in rats.