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 E-2 (PGE(2)) in the hypothalamus and circulating tumor necrosis factor-alpha (TNF-alpha). This investigation was to determine whether central interleukin-10 (IL-10) exerted its antipyresis by reducing changes in circulating TNF-alpha and extracellular glutamate, hydroxyl radicals and PGE(2) 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 PGE(2) in situ. It was found that systemically injected LPS (2 mu g/kg, intravenously) increased the levels of core temperature, and extracellular glutamate, hydroxyl radicals, and PGE(2) in the hypothalamus accompanied by increased plasma levels of TNF-alpha. 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 PGE(2) in the hypothalamus and fever, but not the increased levels of TNF-alpha 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 PGE(2) in the hypothalamus during LPS fever in rabbits. (C) 2011 Elsevier B.V. All rights reserved.