Adrenergic modulation of splenic macrophage cytokine release in polymicrobial sepsis

Deng, Joseph; Muthu, Kuzhali; Gamelli, Richard L.; Shankar, Ravi; Jones, Stephen B.

doi:10.1152/ajpcell.00562.2003

Cited by 72 publications

(45 citation statements)

References 44 publications

(37 reference statements)

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“…This results in the local release of acetylcholine (predominantly from T cells), which binds to a7nAChR on nearby splenic macrophages, reducing their response to noxious stimuli associated with sepsis/endotoxemia. 17,48 Macrophages are a major source of circulating cytokines during inflammation, 20,49 and controlling the behavior of these cells is believed to substantially modulate the systemic immune response. IRI is a sterile form of inflammation that is initiated by the injury/apoptosis of renal cells.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound Prevents Renal Ischemia-Reperfusion Injury by Stimulating the Splenic Cholinergic Anti-Inflammatory Pathway

Gigliotti

Huang

et al. 2013

Journal of the American Society of Nephrology

159

200

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AKI affects both quality of life and health care costs and is an independent risk factor for mortality. At present, there are few effective treatment options for AKI. Here, we describe a nonpharmacologic, noninvasive, ultrasound-based method to prevent renal ischemia-reperfusion injury in mice, which is a model for human AKI. We exposed anesthetized mice to an ultrasound protocol 24 hours before renal ischemia. After 24 hours of reperfusion, ultrasound-treated mice exhibited preserved kidney morphology and function compared with sham-treated mice. Ultrasound exposure before renal ischemia reduced the accumulation of CD11b + Ly6G high neutrophils and CD11b + F4/80 high myeloid cells in kidney tissue. Furthermore, splenectomy and adoptive transfer studies revealed that the spleen and CD4 + T cells mediated the protective effects of ultrasound. Last, blockade or genetic deficiency of the a7 nicotinic acetylcholine receptor abrogated the protective effect of ultrasound, suggesting the involvement of the cholinergic anti-inflammatory pathway. Taken together, these results suggest that an ultrasound-based treatment could have therapeutic potential for the prevention of AKI, possibly by stimulating a splenic anti-inflammatory pathway.

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Section: Discussionmentioning

confidence: 99%

Ultrasound Prevents Renal Ischemia-Reperfusion Injury by Stimulating the Splenic Cholinergic Anti-Inflammatory Pathway

Gigliotti

Huang

et al. 2013

Journal of the American Society of Nephrology

159

200

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“…Macrophages from septic mice are impaired in their capacity to release TNF-α upon ex vivo stimulation with LPS (3,23). We addressed the question whether GM-CSF was able to restore the depressed TNF-α secretion from macrophages of septic mice in comparison to splenic DC.…”

Section: Diverse Responsiveness Of Macrophages and DC To Gm-csf Durinmentioning

confidence: 99%

Diversity of Interferon γ and Granulocyte-Macrophage Colony-Stimulating Factor in Restoring Immune Dysfunction of Dendritic Cells and Macrophages During Polymicrobial Sepsis

Flohé

Agrawal

Flohé

et al. 2008

Mol Med

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The development of immunosuppression during polymicrobial sepsis is associated with the failure of dendritic cells (DC) to promote the polarization of T helper (Th) cells toward a protective Th1 type. The aim of the study was to test potential immunomodulatory approaches to restore the capacity of splenic DC to secrete interleukin (IL) 12 that represents the key cytokine in Th1 cell polarization. Murine polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Splenic DC were isolated at different time points after CLP or sham operation, and stimulated with bacterial components in the presence or absence of neutralizing anti-IL-10 antibodies, murine interferon (IFN) γ, and/or granulocyte macrophage colony-stimulating factor (GM-CSF). DC from septic mice showed an impaired capacity to release the pro-inflammatory and Th1-promoting cytokines tumor necrosis factor α, IFN-γ, and IL-12 in response to bacterial stimuli, but secreted IL-10. Endogenous IL-10 was not responsible for the impaired IL-12 secretion. Up to 6 h after CLP, the combined treatment of DC from septic mice with IFN-γ and GM-CSF increased the secretion of IL-12. Later, DC from septic mice responded to IFN-γ and GM-CSF with increased expression of the co-stimulatory molecule CD86, while IL-12 secretion was no more enhanced. In contrast, splenic macrophages from septic mice during late sepsis responded to GM-CSF with increased cytokine release. Thus, therapy of sepsis with IFN-γ/GM-CSF might be sufficient to restore the activity of macrophages, but fails to restore DC function adequate for the development of a protective Th1-like immune response.

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“…Catecholamines also affect immune cells by suppressing inflammatory responses via macrophages. More importantly, adrenergic receptor signals induce a Th2-type response in T cells and activate B cells [128,129].…”

Section: The Role Of Crf In the Interaction Between Adrenals And The mentioning

confidence: 99%

The corticotropin-releasing factor (CRF) family of peptides as local modulators of adrenal function

Tsatsanis

Dermitzaki

Venihaki

et al. 2007

Cell. Mol. Life Sci.

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Corticotropin-releasing factor (CRF), also termed corticotropin-releasing hormone (CRH) or corticoliberin, is the major regulator of the adaptive response to internal or external stresses. An essential component of the adaptation mechanism is the adrenal gland. CRF regulates adrenal function indirectly through the central nervous system (CNS) via the hypothalamic-pituitary-adrenal (HPA) axis and via the autonomic nervous system by way of locus coeruleus (LC) in the brain stem. Accumulating evidence suggests that CRF and its related peptides also affect the adrenals directly, i.e. not through the CNS but from within the adrenal gland where they form paracrine regulatory loops. Indeed, CRF and its related peptides, the urocortins (UCNs: UCN1, UCN2 and UCN3), their receptors CRF type 1 (CRF(1)) and 2 (CRF(2)) as well as the endogenous pseudo-receptor CRF-binding protein (CRF-BP) are all expressed in adrenal cortical, medullary chromaffin and resident immune cells. The intra-adrenal CRF-based regulatory system is complex and depends on the balance between the local concentration of CRF ligands and the availability of their receptors.

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Adrenergic modulation of splenic macrophage cytokine release in polymicrobial sepsis

Abstract: . Adrenergic modulation of splenic macrophage cytokine release in polymicrobial sepsis.

Cited by 72 publications

References 44 publications

Ultrasound Prevents Renal Ischemia-Reperfusion Injury by Stimulating the Splenic Cholinergic Anti-Inflammatory Pathway

Ultrasound Prevents Renal Ischemia-Reperfusion Injury by Stimulating the Splenic Cholinergic Anti-Inflammatory Pathway

Diversity of Interferon γ and Granulocyte-Macrophage Colony-Stimulating Factor in Restoring Immune Dysfunction of Dendritic Cells and Macrophages During Polymicrobial Sepsis

The corticotropin-releasing factor (CRF) family of peptides as local modulators of adrenal function

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