Effects of tumor necrosis factor α on leptin-sensitive intestinal vagal mechanoreceptors in the cat

The involvement of tumour necrosis factor alpha (TNF-alpha) in inflammatory bowel disease (IBD) has been established, and anti-TNF-alpha has been suggested as a therapeutic approach for the treatment of these pathologies. We studied the effects of TNF-alpha on leptin-sensitive intestinal vagal units to determine whether TNF-alpha exerts its effects through the intestinal vagal mechanoreceptors and to investigate its interactions with substances regulating food intake. The activity of intestinal vagal mechanoreceptors was recorded via microelectrodes implanted into the nodose ganglion in anesthetized cats. TNF-alpha (1 mu g, i.a.) increased the discharge frequency of leptin-activated units (type 1 units; P < 0.05) and had no effect on the discharge frequency of leptin-inhibited units (type 2 units). When TNF-alpha was administered 20 min after sulfated cholecystokinin-8 (CCK), its excitatory effects on type 1 units were significantly enhanced (P < 0.0001) and type 2 units were significantly (P < 0.05) activated. Pre-treatment with Il-1ra (250 mu g, i.a.) blocked the excitatory effects of TNF-alpha on type 1 units whereas the excitatory effects of TNF-alpha administration after CCK treatment on type 2 units were not modified. The activation of leptin-sensitive units by TNF-alpha may explain, at least in part, the weight loss observed in IBD.