Stress-induced suppression of in vivo splenic cytokine production in the rat by neural and hormonal mechanisms

Meltzer, Jonathan C.; MacNeil, Brian; Sanders, Veronica; Pylypas, Susan P.; Jansen, A. H.; Greenberg, Arnold H.; Nance, Dwight M.

doi:10.1016/j.bbi.2003.09.003

Cited by 61 publications

(40 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In vitro experiments with macrophage harvested from spleen and lymph nodes have shown that via β-adrenergic receptors, NE can dramatically inhibit the production and secretion of TNFαin response to LPS (Ignatowski et al, 1996). Less consistent results have been observed for IL-1β production, but NE is generally regarded as inhibitory for this cytokine (Meltzer, et al, 2004). Both inhibitory and facilitatory effects of NE on IL-6 production have been noted, and the direction of the IL-6 response to NE may depend upon the concurrent presence or absence of LPS.…”

Section: Sympathetic Nerves Norepinephrine and The Regulation Of Mamentioning

confidence: 86%

See 1 more Smart Citation

Autonomic innervation and regulation of the immune system (1987–2007)

Nance¹,

Sanders²

2007

Brain, Behavior, and Immunity

Self Cite

746

580

View full text Add to dashboard Cite

Since 1987, only a few neuroanatomical studies have been conducted to identify the origin of innervation for the immune system. These studies demonstrated that all primary and secondary immune organs receive a substantial sympathetic innervation from sympathetic postganglionic neurons. Neither the thymus nor spleen receive any sensory neural innervation; however, there is evidence that lymph nodes and bone marrow may be innervated by sensory neurons located in dorsal root ganglia. There is no neuroanatomical evidence for a parasympathetic or vagal nerve supply to any immune organ. Thus, the primary pathway for the neural regulation of immune function is provided by the sympathetic nervous system (SNS) and its main neurotransmitter, norepinephrine (NE). Activation of the SNS primarily inhibits the activity of cells associated with the innate immune system, while it either enhances or inhibits the activity of cells associated with the acquired/adaptive immune system. Innate immune cells express both alpha and beta-adrenergic receptor subtypes, while T and B lymphocytes express adrenergic receptors of the beta2 subtype exclusively, except for murine Th2 cells that lack expression of any subtype. Via these adrenergic receptors, NE is able to regulate the level of immune cell activity by initiating a change in the level of cellular activity, which often involves a change in the level of gene expression for cytokines and antibodies.

show abstract

Section: Sympathetic Nerves Norepinephrine and The Regulation Of Mamentioning

confidence: 86%

“…A brief (15 minute) bout of intermittent footshock was used to examine the sympathetic regulation of splenic macrophage function in rats (Meltzer et al, 2004). Both splenic and plasma levels of inflammatory cytokines were measured in response to i.v.…”

Section: Effects Of Stress On Splenic Macrophagesmentioning

confidence: 99%

Autonomic innervation and regulation of the immune system (1987–2007)

Nance¹,

Sanders²

2007

Brain, Behavior, and Immunity

Self Cite

746

580

View full text Add to dashboard Cite

show abstract

“…Although less is known about the central mechanisms that modulate iNOS expression in peripheral tissues such as the spleen, liver, and lung, the sympathetic nervous system may likewise play a major role. Interestingly, stress-induced suppression splenic cytokine responses to LPS were shown to be mediated by the sympathetic nervous system (Meltzer et al, 2004). Given the many similarities between the effects of stress and exogenous opioids on immune function, it is tempting to speculate that similar mechanisms mediate heroin's effect on nitric oxide production.…”

Section: Discussionmentioning

confidence: 99%

Evidence for the Nucleus Accumbens as a Neural Substrate of Heroin-Induced Immune Alterations

Saurer

Ijames²,

Lysle³

2009

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Administration of opioid drugs such as heroin produces several immunosuppressive effects, including decreases in natural killer (NK) cell activity, lymphocyte proliferative responses, and nitric oxide production. Interestingly, opioids have been shown to alter many immune parameters indirectly by modulating the immunoregulatory actions of the central nervous system. Recently, it has been demonstrated that morphine inhibits NK cell activity through a neural pathway that requires the activation of dopamine D 1 receptors in the nucleus accumbens shell. The present study examined whether the nucleus accumbens also mediates the effects of heroin, a more commonly abused opioid, on several parameters of immune status in Lewis rats. The results showed that bilateral administration of the dopamine D 1 receptor antagonist R-(ϩ)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH-23390; 0.015 and 0.15 g/side) into the nucleus accumbens shell blocked decreases in splenic NK activity produced by heroin (3 mg/kg s.c.) but did not attenuate the suppression of splenocyte proliferative responses to concanavalin-A or lipopolysaccharide (LPS). A subsequent experiment was performed to evaluate the effect of D 1 receptor antagonism on LPS-induced expression of inducible nitric-oxide synthase (iNOS) in vivo. These results showed that intra-accumbens SCH-23390 administration prevented heroin-induced reductions of iNOS mRNA expression in spleen, liver, and lung tissues and attenuated the suppression of nitric oxide levels in plasma. Collectively, these findings indicate that nucleus accumbens dopamine D 1 receptors are critically involved in heroin-induced immune alterations.Opioid drug use is associated with adverse health consequences. Heroin abusers display abnormalities in basic immune parameters and have high rates of viral, bacterial, and fungal infections (Louria et al., 1967;Govitrapong et al., 1998). Although the high incidence of infectious diseases among abusers is commonly attributed to increased pathogen exposure or insalubrious behaviors, opioids exert potent immunomodulatory effects that may further enhance infection susceptibility. Controlled studies in humans demonstrate that morphine produces immunosuppressive effects in healthy, nondrug-using subjects (Yeager et al., 1995), and clinical reports indicate that higher doses of opioid analgesics are associated with greater frequencies of infectious complications among burn victims and patients that underwent cardiac surgery (El Solh et al., 2006;Schwacha et al., 2006). Thus, the use of opioids, whether for therapeutic or recreational purposes, may directly influence resistance to infectious diseases.In animal models, morphine has been shown to suppress a variety of immune parameters, but the mechanisms underlying these effects are not fully understood Lockwood et al., 1994). Opioids modulate immunity in a highly complex manner by interacting with opioid receptors expressed by multiple cell types throughout the body. For exa...

show abstract

“…This study identified possible mechanisms that might be involved in the suppression of monocyte expression of TNF-␣ and IL-6 after cocaine and its metabolites have cleared from the circulation and found that in vivo estimates of sympathetic activity (i.e., LF/HF ratio) negatively correlated with resting and LPS-stimulated monocyte production of TNF-␣ but not IL-6. Moreover, sympathetic activation induces a more robust inhibition of LPS-stimulated production of TNF-␣ than other proinflammatory cytokines (Elenkov et al, 2000;Meltzer et al, 2004). IL-6 and TNF-␣ gene expression are modulated by some common signaling pathways (e.g., nuclear factor-B), but each gene is also regulated by distinct transcription control pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Given evidence that proinflammatory cytokines show a marked diurnal variation (Redwine et al, 2000), differences between cocaine-dependent men versus control subjects were examined over a 24-h period, whereas the action of acute cocaine was profiled over 48 h. Finally, we evaluated a potential mechanism for decreases of resting and stimulated monocyte expression of TNF-␣ and IL-6 in cocaine dependence by assessing variations in sympathetic and parasympathetic nervous system activity as estimated by heart rate variability (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996). Cocaine is reported to induce increases in sympathetic effector mechanisms (Jacobsen et al, 1997), and sympathetic neurotransmitters are known to inhibit proinflammatory cytokine secretion (Friedman and Irwin, 1997;Straub et al, 2000;Meltzer et al, 2004).…”

mentioning

confidence: 99%

Cocaine Dependence and Acute Cocaine Induce Decreases of Monocyte Proinflammatory Cytokine Expression across the Diurnal Period: Autonomic Mechanisms

Irwin¹,

Olmos²,

Wang³

et al. 2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Cocaine dependence is associated with an increased risk of infectious diseases. The innate immune system triggers effector pathways to combat microbial pathogens through expression of tumor necrosis factor-␣ (TNF-␣) and interleukin-6 (IL-6). It is not known whether cocaine alters the capacity of monocytes to respond to a bacterial challenge in humans. In cocaine-dependent volunteers and control subjects, we analyzed monocyte TNF-␣ and IL-6 expression at rest and in response to the bacterial ligand, lipopolysaccharide (LPS), over a 24-h period. In addition, the in vivo effects of cocaine (40 mg) versus placebo on monocyte expression of TNF-␣ and IL-6 were profiled over 48 h. Cocaine-dependent volunteers showed a decrease in the capacity of monocytes to express TNF-␣ and IL-6 compared with control subjects. Moreover, acute infusion of cocaine induced a further decline in the responsiveness of monocytes to LPS, which persisted after cocaine had cleared from the blood. Heart rate variability analyses showed that increases of sympathetic activity along with vagal withdrawal were associated with decreases in monocyte expression of TNF-␣. Cocaine alters autonomic activity and induces protracted decreases in innate immune mechanisms. Targeting sympathovagal balance might represent a novel strategy for partial amelioration of impairments of innate immunity in cocaine dependence.

show abstract

Stress-induced suppression of in vivo splenic cytokine production in the rat by neural and hormonal mechanisms

Cited by 61 publications

References 40 publications

Autonomic innervation and regulation of the immune system (1987–2007)

Autonomic innervation and regulation of the immune system (1987–2007)

Evidence for the Nucleus Accumbens as a Neural Substrate of Heroin-Induced Immune Alterations

Cocaine Dependence and Acute Cocaine Induce Decreases of Monocyte Proinflammatory Cytokine Expression across the Diurnal Period: Autonomic Mechanisms

Contact Info

Product

Resources

About