Local inhibition of LPS-induced hypothalamic TNF-formation by pentoxifylline has no effect on production of Il-6 within the anterior hypothalamus

Push-pull perfusions of the anterior hypothalamus were performed in four gr oups of guinea pigs characterized as follows: (a) hypothalamus perfused wit h artificial cerebrospinal fluid (CSF), intramuscular (im) injection of 20 mu g/kg bacterial lipopolysaccharide (LPS); (b) hypothalamus perfused with CSF, im injection of saline; (c) hypothalamus perfused with CSF which conta ined 0.1 mu g/mu l pentoxifylline, im injection of LPS; (d) hypothalamus pe rfused with CSF which contained 0.1 mu g/mu l pentoxifylline, im injection of saline. Injection of LPS resulted in a significant rise of hypothalamic tumor necrosis factor-alpha (TNF), 60 min and 180 min after administration of LPS compared to the value measured 60 min before LPS was injected. In an imals injected with saline, the baseline level of TNF in hypothalamic perfu sates remained manifest. Perfusion of the anterior hypothalamus with CSF wh ich contained 0.1 mu g/mu l pentoxifylline resulted in a complete suppressi on of hypothalamic TNF formation and release in animals injected with LPS o r saline. The LPS-induced rise of hypothalamic interleukin-6 (IL-6) was the same in guinea-pigs perfused with CSF or CSF plus pentoxifylline. The LPS- induced rise of rectal temperature, measured about 3 h after LPS injection (fever peak) was the same in guinea-pigs perfused with CSF or CSF plus pent oxifylline. The results indicate that the hypothalamic rise of IL-6 and the febrile temperature peak in response to peripheral injection of LPS does n ot depend on the local formation of TNF within the anterior hypothalamus. ( C) 2000 Elsevier Science Ltd. All rights reserved.