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      Central Sympathetic Modulation of Tissue Cytokine Response to Hemorrhage

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          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.

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          Most cited references 7

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          Epidemiology of trauma deaths.

          The records of all 437 persons who died from trauma in San Francisco in 1977 were examined. Sixty-five percent of the sample (285 younger than 50 years, and 119 were between ages 21 and 30. Gunshot wounds (140 or 32 percent) and falls (122 or 28 percent) were the most common causes of injury. Fifty-three percent of the sample were dead at the scene of injury before transport could be accomplished, 7.5 percent died in the emergency room, and 39.5 percent died in the hospital. Fifty-five percent of the 359 patients who died within the first 2 days died from brain injury, while 78 percent of the 55 late deaths were due to sepsis and multiple organ failure. In 10 cases (2 percent), death was due to delayed transport or to errors in diagnosis and treatment and was deemed preventable. The key areas in which advances are necessary in order to reduce the number of trauma deaths are prevention of trauma, more rapid and skilled transport of injured victims, better early management of primary brain injuries, and more effective treatment of the late complications of sepsis and multiple organ failure.
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            The effect of norepinephrine on endotoxin-mediated macrophage activation

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              The effects of stress on splenic immune function are mediated by the splenic nerve.

              Intermittent footshock (FS) suppresses immune function of spleen cells. To determine if the autonomic nervous system mediates this immunosuppression in spleen cells, we tested whether cutting the splenic nerve, which depletes splenic norepinephrine levels by 98-100% and eliminates catecholamine fibers, blocks the effects of stress. Splenic nerve sections, sham operations, or no surgery were performed on male Sprague-Dawley rats. Ten days later, rats were injected with sheep red blood cells (SRBC). Three days later, rats were placed in a chamber equipped with a shock grid. Foot shock (1.6 mA) was administered for 5 s on a VI 3.5 min schedule for 60 min. Each FS was preceded by a 15-s warning tone. Controls were treated identically except for the FS. The next day spleen cells were harvested and the number of IgM plaque-forming cells (PFCs) determined. For the sham and unoperated control animals, the number of PFCs was reduced for the stressed animals relative to the nonstressed controls, and there was no effect of the sham surgeries. In contrast, there was no difference between the stressed and nonstressed groups in which the splenic nerve had been sectioned, and their PFC response was comparable to the controls. Next we examined the effects of FS on the proliferative response to mitogens (PHA and ConA) following splenic nerve sections or sham operations. One week following surgery, animals were given a 60-min session of FS or exposed to the chamber/tone without FS. Rats were then killed, spleens harvested, and the proliferative response to mitogens determined.(ABSTRACT TRUNCATED AT 250 WORDS)

                Author and article information

                S. Karger AG
                June 1999
                16 April 1999
                : 6
                : 3
                : 193-200
                Department of Surgery, North Shore University Hospital, Manhasset, N.Y., and Department of Medicine, Brookhaven National Laboratory, Upton, N.Y., USA
                26382 Neuroimmunomodulation 1999;6:193–200
                © 1999 S. Karger AG, Basel

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                Page count
                Figures: 5, References: 49, Pages: 8
                Original Paper


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