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
✍ Scribed by Carlos R. Plata-Salamán; Sergey E. Ilyin
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 111 KB
- Volume
- 49
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Interleukin
-1 (IL-1) induces anorexia, fever, sleep changes, and neuroendocrine alterations when administered into the brain. Here, we investigated the regulation of the IL-1 system (ligand, receptors, receptor accessory protein, and receptor antagonist), tumor necrosis factor-␣ (TNF-␣), transforming growth factor (TGF)-1, and TGF-␣ mRNAs in the hypothalamus of obese (fa/fa) and lean (Fa/Fa) Zucker rats in response to the intracerebroventricular microinfusion of IL-1 (8.0 ng/24 hr for 72 hr, a dose that yields estimated pathophysiological concentrations in the cerebrospinal fluid). IL-1 increased IL-1, 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-␣, and TGF-1 mRNAs in the hypothalamus from obese and lean rats. IL-1-induced IL-1 system and ligand (IL-1, TNF-␣, and TGF-1) mRNA profiles were highly intercorrelated in the same samples. Levels of membrane-bound IL-1R AcP and TGF-␣ mRNAs did not change. Heat-inactivated IL-1 had no effect. The data suggest 1) the operation of an IL-1 feedback system (IL-1/IL-1RI/IL-1R Acp II/ IL-1RII/IL-1Ra) and 2) potential cytokine-cytokine interactions with positive (IL-1 & TNF-␣) and negative (TGF-1 = IL-1/TNF-␣) feedback. Dysregulation of the IL-1 feedback system and the TGF-1/ IL-1-TNF-␣ balance may have implications for neurological disorders associated with high levels of IL-1 in the brain.