Central interleukin-10 attenuated lipopolysaccharide-induced changes in core temperature and hypothalamic glutamate, hydroxyl radicals and prostaglandin-E2

It has been documented that intravenous lipopolysaccharide (LPS) in rabbits causes fever accompanied by increased levels of extracellular glutamate, hydroxyl radicals, and prostaglandin E2 (PGE2) in the hypothalamus and circulating tumor necrosis factor-alpha (TNF-α). This investigation was to determine whether central interleukin-10 (IL-10) exerted its antipyresis by reducing changes in circulating TNF-α and extracellular glutamate, hydroxyl radicals and PGE2 in the hypothalamus. The microdialysis probes were stereotaxically and chronically implanted into the preoptic anterior hypothalamus of rabbit brain for determinating extracellular glutamate, hydroxyl radicals, and PGE2 in situ. It was found that systemically injected LPS (2 μg/kg, intravenously) increased the levels of core temperature, and extracellular glutamate, hydroxyl radicals, and PGE2 in the hypothalamus accompanied by increased plasma levels of TNF-α. Pretreatment with IL-10 (10-100 ng, intracerebroventricularly) 1 h before intravenous LPS significantly reduced the LPS-induced changes in extracellular glutamate, hydroxyl radicals, and PGE2 in the hypothalamus and fever, but not the increased levels of TNF-α in rabbits. These findings suggested that directly injected IL-10 into the lateral cerebral ventricle 1 h before intravenous LPS exerted its antipyresis by inhibiting the changes in extracellular glutamate, hydroxyl radicals and PGE2 in the hypothalamus during LPS fever in rabbits.