Interleukin-1β (IL-1β)-induced modulation of the hypothalamic IL-1β system,tumor necrosis factor-α, and transforming growth factor-β1 mRNAs in obese (fa/fa) and lean (Fa/Fa) Zucker rats: Implications to IL-1β feedback systems and cytokine–cytokine interactions

Interleukin-1β (IL-1β) induces anorexia, fever, sleep changes, and neuroendocrine alterations when administered into the brain. Here, we investigated the regulation of the IL-1β system (ligand, receptors, receptor accessory protein, and receptor antagonist), tumor necrosis factor-α (TNF-α), transforming growth factor (TGF)-β1, and TGF-α mRNAs in the hypothalamus of obese (fa/fa) and lean (Fa/Fa) Zucker rats in response to the intracerebroventricular microinfusion of IL-1β (8.0 ng/24 hr for 72 hr, a dose that yields estimated pathophysiological concentrations in the cerebrospinal fluid). IL-1β increased IL-1β, IL-1 receptor types I and II (IL-1RI and IL-1RII), IL-1 receptor accessory protein soluble form (IL-1R AcP II), IL-1 receptor antagonist (IL-1Ra), TNF-α, and TGF-β1 mRNAs in the hypothalamus from obese and lean rats. IL-1β–induced IL-1β system and ligand (IL-1β, TNF-α, and TGF-β1) mRNA profiles were highly intercorrelated in the same samples. Levels of membrane-bound IL-1R AcP and TGF-α mRNAs did not change. Heat-inactivated IL-1β had no effect. The data suggest 1) the operation of an IL-1β feedback system (IL-1β/IL-1RI/IL-1R Acp II/IL-1RII/IL-1Ra) and 2) potential cytokine–cytokine interactions with positive (IL-1β ←→ TNF-α) and negative (TGF-β1 → IL-1β/TNF-α) feedback. Dysregulation of the IL-1β feedback system and the TGF-β1/IL-1β-TNF-α balance may have implications for neurological disorders associated with high levels of IL-1β in the brain. J. Neurosci. Res. 49:541–550, 1997. © 1997 Wiley-Liss, Inc.