DIFFERENTIAL-EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA AND TUMOR-NECROSIS-FACTOR-BETA ON RAT VENTROMEDIAL HYPOTHALAMIC NEURONS IN-VITRO

The effects of tumor necrosis factor (TNF)-alpha and -beta on the spon taneous firing rate of ventromedial hypothalamic (VMH) neurons were ex amined in rat brain slice preparations. Of 89 neurons, 36 (40%) showed a decrease in the firing rate to -78.2 +/- 4.0% (n = 36, mean +/- SE) of the preapplication level after a bath application of 20 ng/ml (sim ilar to 1.2 nM) of TNF-alpha. This response to TNF-alpha still persist ed in a low-Ca2+, high-Mg2+ medium. Six (7%) of the 89 neurons were ex cited and 47 (53%) were unaffected by TNF-alpha. The inhibitory respon ses induced by TNF-alpha were abolished in a solution that contained s odium salicylate (1.9 x 10(-8) M). In contrast, TNF-beta at a dose of 20 ng/ml (similar to 1.1 nM) increased the firing rate to +39.2 +/- 6. 5% (n = 11) of the preapplication level in 11 (24.5%) of 45 VMH neuron s. Two of the 45 neurons (4.5%) were inhibited and 32 (71%) were unaff ected by TNF-beta. The threshold concentration of TNF-alpha to alter t he VMH neuron activity was lower than that of TNF-beta. Heat-inactivat ed TNFs were without effect. These findings suggest that TNF-alpha and -beta act as neuro-modulators in the VMH, at least partly through pro staglandin synthesis, and differentially modulate the VMH neuron activ ity.