| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Research Abstract |
Although interleukin-l (IL-l), interferon- (IFN ), and tumor necrosis factor (TNF), which are derived from macrophages and leucocytes, primarily work as regulators within the immune system, recent findings have demonstrated that these immuno- regulators produce non-immunological host defense response (fever, anorexia,sleep, induction of acute phase proteins, and the modification of immune systems), some of which are mediated by their actions on the brain. We investigated the effects of local application of IL-l, recombinant human IFN 2, and recombinant human TNF on the unit activity of neurons in the preoptic and anterior hypothalamus (PO/AH) and the hypothalamic ventromedial nucleus (VMH) of the rat. Local application of IL-l and IFN 2 predominantly decreased the activity of PO/AH warm-sensitive neurons and increased the activity of PO/AH cold-sensitive neurons, but did not affect the majority of thermally insensitive neurons. THF also produced similar responses in PO/AH thermosensitive neurons. These neuronal responses may explain the thermoregulatory changes during the development of fever. The neuronal responses to IL-l were blocked by mepacrine, a phospholipase-A2 inhibitor, and by sodium salicylate, suggesting the involvement of cyclooxygenase metabolies of arachidonate. However, salicylate failed to affect the neuronal responses to IFN , but naloxone could reversibly block them. This is consistent with the previous findings that IFN bind opiate receptors in the mouse brain. IFN increased the activity of VMH neurons, some of which were glucosensitive, and the effect was blocked by naloxone. This may explain, at least in part, anorexia during IFN therapy. This results suggest that IL-l, IFN , and TNF serve as chemical mes-sengers from the immune system to the brain during invasion of microorganisms and antigens, injury, and inflammation, and thus they may provide an afferent link for the proposed regulatory circuits between the brain and the immune system.
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