Central Sympathetic Modulation of Tissue Cytokine Response to Hemorrhage

Abstract

Hemorrhage is associated with altered immune responses as well as with early increases in circulating levels and tissue content of proinflammatory cytokines. The present study determined the effects of central chemical sympathectomy on the early increase in tissue content of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) following fixed-pressure (40 mm Hg) hemorrhage as well as on the associated activation of the opiate and glucocorticoid systems. Conscious unrestrained nonheparinized male Sprague-Dawley rats were randomized to receive either 6-hydroxydopamine intracerebroventricularly or equal volumes of saline (5 µl). Half of the animals in each group underwent hemorrhage followed by fluid resuscitation with lactated Ringer’s solution, and were sacrificed at completion of the resuscitation period. Hemorrhage elevated TNF-α and IL-6 content in spleen (30–47%) and lung (∼40%). Central chemical sympathectomy did not alter tissue cytokine content or circulating levels of β-endorphin and corticosterone. However, central chemical sympathectomy attenuated the hemorrhage-induced increase in lung and spleen TNF-α, enhanced the IL-6 response in spleen and blunted the rise in circulating β-endorphin levels. These results demonstrate central modulation of the inflammatory and opiate responses to hemorrhagic stress.