Human recombinant tumor necrosis factor and interferon affect the activity of neurons in the organum vasculosum laminae terminalis.
It is generally thought that fever is induced by blood-borne cytokines via an action on hypothalamic thermosensitive neurons. Recent studies suggest that the organum vasculosum laminae terminalis (OVLT), which lacks the blood-brain barrier, may be necessary for fever induction by systemic pyrogens. We have examined the responses of neurons in the OVLT to the pyrogenic cytokines, human recombinant tumor necrosis factor alpha (TNF) and interferon alpha 2 (IFN), by recording extracellular single-units in brain slice preparations from guinea pigs. Of all the OVLT neurons tested with TNF (900-5000 ng/ml perfusate/min) and IFN (1200-8500 units/ml perfusate/min), administered for 2.5 min, 44% increased their firing rates (FR) for 30.6-57.5 min (average, 47.4 min) with onset latencies of 6.1-9.8 min (average, 7.9 min). The remaining 56% of the neurons did not change their FR after TNF or IFN. Carrier vehicles for these cytokines produced no FR change. The results suggest the possibility that the OVLT may be a site where chemical signals of blood-borne cytokines are transduced into neuronal signals.
Shibata
M
M
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.
Blatteis
C M
CM
D000818:Animals; D002552:Cerebral Ventricles / Q000166:cytology / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology; D016898:Interferon-alpha / Q000502:physiology*; D008839:Microelectrodes; D009474:Neurons / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha