Interleukin-1beta (IL-1beta)-induced modulation of the hypothalamic IL-1beta system, tumor necrosis factor-alpha, and transforming growth factor-beta1 mRNAs in obese (fa/fa) and lean (Fa/Fa) Zucker rats: implications to IL-1beta feedback systems and cytokine-cytokine interactions.
Interleukin-1beta (IL-1beta) induces anorexia, fever, sleep changes, and neuroendocrine alterations when administered into the brain. Here, we investigated the regulation of the IL-1beta system (ligand, receptors, receptor accessory protein, and receptor antagonist), tumor necrosis factor-alpoha (TNF-alpha), transforming growth factor (TGF)-beta1, and TGF-alpha mRNAs in the hypothalamus of obese (fa/fa) and lean (Fa/Fa) Zucker rats in response to the intracerebroventricular microinfusion of IL-1beta (8.0 ng/24 hr for 72 hr, a dose that yields estimated pathophysiological concentrations in the cerebrospinal fluid). IL-1beta increased IL-1beta, 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-alpha, and TGF-beta1 mRNAs in the hypothalamus from obese and lean rats. IL-1beta-induced IL-1beta system and ligand (IL-1beta, TNF-alpha, and TGF-beta1) mRNA profiles were highly intercorrelated in the same samples. Levels of membrane-bound IL-1R AcP and TGF-alpha mRNAs did not change. Heat-inactivated IL-1beta had no effect. The data suggest 1) the operation of an IL-1beta feedback system (IL-1beta/IL-1RI/IL-1R Acp II/IL-1RII/IL-1Ra) and 2) potential cytokine-cytokine interactions with positive (IL-1beta <--> TNF-alpha) and negative (TGF-beta1 --> IL-1beta/TNF-alpha) feedback. Dysregulation of the IL-1beta feedback system and the TGF-beta1/IL-1beta-TNF-alpha balance may have implications for neurological disorders associated with high levels of IL-1beta in the brain.
Plata-Salamán
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CR
Division of Molecular Biology, School of Life and Health Sciences, University of Delaware, Newark 19716-2590, USA. crps@udel.edu
Ilyin
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SE
D000818:Animals; D005246:Feedback / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D016211:Transforming Growth Factor alpha / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D007375:Interleukin-1; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta