Hyperthermia-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system

Ganta, Chanran; Blecha, Frank; Ganta, Roman R.; Helwig, Bryan G.; Parimi, Sujatha; Lü, Nonghua; Fels, Richard J.; Musch, Timothy I.; Kenney, Michael J.

doi:10.1152/physiolgenomics.00109.2004

Cited by 20 publications

(30 citation statements)

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“…In recent studies, we found that whole body hyperthermia and central ANG II infusion increased both the level of splenic sympathetic nerve activity and the expression of selective splenic cytokine and chemokine genes (19,20). The enhanced splenic gene expression to these interventions was abrogated by denervation of splenic sympathetic nerves, suggesting a role for splenic sympathoexcitation in upregulation of selective splenic cytokine genes.…”

Section: Discussionmentioning

confidence: 84%

“…For monitoring during the experiment and for subsequent data analysis, the filtered neurograms were routed to an oscilloscope and a nerve traffic analyzer. Sympathetic nerve potentials were full-wave rectified, integrated (time constant 10 ms) and quantified as volts ϫ seconds (V ⅐ s) (19,20,28,29). SND was corrected for background noise after administration of the ganglionic blocker, trimethaphan camsylate (10 -15 mg/kg iv).…”

Section: Methodsmentioning

confidence: 99%

“…Results of our recent studies demonstrate that in rats with intact splenic nerves, whole body hyperthermia (19) and central ANG II infusion (20) increase splenic sympathetic nerve discharge (SND) and the expression of selective splenic cytokine genes. Splenic cytokine gene expression responses to whole body hyperthermia and central ANG II infusion are significantly reduced in splenic nerve-denervated compared with splenic nerve-intact rats (19,20), suggesting that activation of splenic SND can enhance splenic cytokine gene expression.Hypothermia, a common side effect of extreme cold environments, anesthesia, and serious traumatic injuries, alters the sympathetic nervous system and immune system regulation (8, 13-15, 21, 27-29, 47-50). Acute cold stress increases plasma concentrations of norepinephrine and epinephrine (18,26,46,52), changes the pattern of synchronized SND bursts (28), influences the frequency-domain relationships between discharge bursts in regionally selective sympathetic nerves (28), and produces nonuniform changes in the level of sympathetic nerve activity to selected target organs (28).…”

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confidence: 96%

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confidence: 96%

“…Splenic cytokine gene expression responses to whole body hyperthermia and central ANG II infusion are significantly reduced in splenic nerve-denervated compared with splenic nerve-intact rats (19,20), suggesting that activation of splenic SND can enhance splenic cytokine gene expression.…”

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confidence: 96%

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Hypothermia-enhanced splenic cytokine gene expression is independent of the sympathetic nervous system

Ganta

Helwig²,

Blecha³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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. Hypothermia-enhanced splenic cytokine gene expression is independent of the sympathetic nervous system. Am J Physiol Regul Integr Comp Physiol 291: R558 -R565, 2006. First published February 9, 2006 doi:10.1152/ajpregu.00846.2005.-Splenic nerve denervation abrogates enhanced splenic cytokine gene expression responses to acute heating, demonstrating that hyperthermia-induced activation of splenic sympathetic nerve discharge (SND) increases splenic cytokine gene expression. Hypothermia alters SND responses; however, the role of the sympathetic nervous system in mediating splenic cytokine gene expression responses to hypothermia is not known. The purpose of the present study was to determine the effect of hypothermia on the relationship between the sympathetic nervous system and splenic cytokine gene expression in anesthetized F344 rats. Gene expression analysis was performed using a microarray containing 112 genes, representing inflammatory cytokines, chemokines, cytokine/chemokine receptors and housekeeping genes. A subset of differentially expressed genes was verified by real-time RT-PCR analysis. Splenic SND was decreased significantly during cooling (core temperature decreased from 38 to 30°C) in splenicintact rats but remained unchanged in sham-cooled splenic-intact rats (core temperature maintained at 38°C). Hypothermia upregulated the transcripts of several genes, including, chemokine ligands CCL2, CXCL2, CXCL10, and CCL20, and interleukins IL-1␣, IL-1␤, and IL-6. Gene expression responses to hypothermia were similar for the majority of cytokine genes in splenic-intact and splenic-denervated rats. These results suggest that hypothermia-enhanced splenic cytokine gene expression is independent of splenic SND.hypothermia; splenic cytokine gene expression; splenic sympathetic nerve discharge EVIDENCE FROM THE DISCIPLINES of neuroscience and immunology demonstrate bidirectional communication pathways between the sympathetic nervous system and the immune system (2, 3, 13, 38). Sympathetic innervation to the spleen provides a connection between central sympathetic neural circuits and immunocompetent cells in the spleen (1,6,9,16,17). For example, chemical sympathectomy alters splenic T and B cell proliferation and natural killer cell activity (36 -40, 45) and diminishes splenic production of immunoglobulin M (31). Results of our recent studies demonstrate that in rats with intact splenic nerves, whole body hyperthermia (19) and central ANG II infusion (20) increase splenic sympathetic nerve discharge (SND) and the expression of selective splenic cytokine genes. Splenic cytokine gene expression responses to whole body hyperthermia and central ANG II infusion are significantly reduced in splenic nerve-denervated compared with splenic nerve-intact rats (19,20), suggesting that activation of splenic SND can enhance splenic cytokine gene expression.Hypothermia, a common side effect of extreme cold environments, anesthesia, and serious traumatic injuries, alters the sympathetic nervous system and immune system regula...

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Section: Discussionmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 96%

mentioning

confidence: 96%

mentioning

confidence: 96%

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Hypothermia-enhanced splenic cytokine gene expression is independent of the sympathetic nervous system

Ganta

Helwig²,

Blecha³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Autonomic Nervous System and Immune System Interactions

Kenney

Ganta

2014

Comprehensive Physiology

294

218

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The present review assesses the current state of literature defining integrative autonomic-immune physiological processing, focusing on studies that have employed electrophysiological, pharmacological, molecular biological and central nervous system experimental approaches. Central autonomic neural networks are informed of peripheral immune status via numerous communicating pathways, including neural and non-neural. Cytokines and other immune factors affect the level of activity and responsivity of discharges in sympathetic and parasympathetic nerves innervating diverse targets. Multiple levels of the neuraxis contribute to cytokine-induced changes in efferent parasympathetic and sympathetic nerve outflows, leading to modulation of peripheral immune responses. The functionality of local sympathoimmune interactions depends on the microenvironment created by diverse signaling mechanisms involving integration between sympathetic nervous system neurotransmitters and neuromodulators; specific adrenergic receptors; and the presence or absence of immune cells, cytokines and bacteria. Functional mechanisms contributing to the cholinergic anti-inflammatory pathway likely involve novel cholinergic-adrenergic interactions at peripheral sites, including autonomic ganglion and lymphoid targets. Immune cells express adrenergic and nicotinic receptors. Neurotransmitters released by sympathetic and parasympathetic nerve endings bind to their respective receptors located on the surface of immune cells and initiate immune-modulatory responses. Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions. Further understanding of regulatory mechanisms linking the sympathetic nervous, parasympathetic nervous, and immune systems is critical for understanding relationships between chronic disease development and immune-associated changes in autonomic nervous system function.

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Heat Stroke

Leon

Bouchama

2015

Comprehensive Physiology

360

356

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Heat stroke is a life-threatening condition clinically diagnosed as a severe elevation in body temperature with central nervous system dysfunction that often includes combativeness, delirium, seizures, and coma. Classic heat stroke primarily occurs in immunocompromised individuals during annual heat waves. Exertional heat stroke is observed in young fit individuals performing strenuous physical activity in hot or temperature environments. Long-term consequences of heat stroke are thought to be due to a systemic inflammatory response syndrome. This article provides a comprehensive review of recent advances in the identification of risk factors that predispose to heat stroke, the role of endotoxin and cytokines in mediation of multi-organ damage, the incidence of hypothermia and fever during heat stroke recovery, clinical biomarkers of organ damage severity, and protective cooling strategies. Risk factors include environmental factors, medications, drug use, compromised health status, and genetic conditions. The role of endotoxin and cytokines is discussed in the framework of research conducted over 30 years ago that requires reassessment to more clearly identify the role of these factors in the systemic inflammatory response syndrome. We challenge the notion that hypothalamic damage is responsible for thermoregulatory disturbances during heat stroke recovery and highlight recent advances in our understanding of the regulated nature of these responses. The need for more sensitive clinical biomarkers of organ damage is examined. Conventional and emerging cooling methods are discussed with reference to protection against peripheral organ damage and selective brain cooling.

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Hyperthermia-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system

Cited by 20 publications

References 57 publications

Hypothermia-enhanced splenic cytokine gene expression is independent of the sympathetic nervous system

Hypothermia-enhanced splenic cytokine gene expression is independent of the sympathetic nervous system

Autonomic Nervous System and Immune System Interactions

Heat Stroke

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