GM-CSF counteracts hemorrhage-induced suppression of cytokine-producing capacity

Husain, Baher; Lendemans, Sven; Ackermann, M.; Wendel, Albrecht; Schade, F. Ulrich; Flohé, Sascha

doi:10.1007/s00011-003-1216-2

Cited by 5 publications

(5 citation statements)

References 40 publications

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“…In view of this, it appears that rats might also have different plasma IL-10 kinetics than mice, which explains the difference between our present findings and those of the previous study. The present results also showed that the production capacity of proinflammatory cytokines, IL-6 and TNF-␣, was increased by Kupffer cells, but their production by splenic macrophages, alveolar macrophages, and PBMC was decreased following trauma-hemorrhage, consistent with the previous findings (4,14,23,38). Moreover, the production capacity of the antiinflammatory cytokine IL-10 by Kupffer cells, splenic macrophages, alveolar macrophages, and PBMC was increased.…”

Section: Discussionsupporting

confidence: 92%

Tissue compartment-specific role of estrogen receptor subtypes in immune cell cytokine production following trauma-hemorrhage

Suzuki

Shimizu

et al. 2007

Journal of Applied Physiology

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Although 17beta-estradiol administration following trauma-hemorrhage attenuates plasma cytokines and alteration in immune cell cytokine production, it is not known whether the salutary effects are mediated via estrogen receptor (ER)-alpha or ER-beta. Accordingly, we examined which ER subtype predominantly mediates the salutary effects of 17beta-estradiol on systemic inflammatory response/immune cell cytokine production in various tissues following trauma-hemorrhage. Male rats underwent trauma-hemorrhage (mean blood pressure: 40 mmHg for 90 min) and fluid resuscitation. The ER-alpha agonist propyl pyrazole triol (PPT; 5 microg/kg), the ER-beta agonist diarylpropionitrile (DPN; 5 microg/kg), 17beta-estradiol (50 microg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation, and various measurements were made 24 h thereafter. 17beta-Estradiol or PPT administration following trauma-hemorrhage prevented the increase in plasma IL-6 and IL-10 levels that were observed in vehicle-treated animals. IL-6 and TNF-alpha production by Kupffer cells increased; however, splenic macrophages (SMPhi), alveolar macrophages (AMPhi), and peripheral blood mononuclear cells (PBMC) had decreased release of these cytokines after trauma-hemorrhage. IL-10 production, however, increased in all macrophage populations. Administration of 17beta-estradiol following trauma-hemorrhage prevented all of these alterations. PPT had the same effects as 17beta-estradiol on IL-6 and TNF-alpha production by Kupffer cells and SMPhi, and DPN had the same effects on AMPhi and PBMC. The same effects as 17beta-estradiol on IL-10 production were observed by PPT on Kupffer cells and DPN on PBMC. Both agonists were equally effective on SMPhi and AMPhi. Thus ER subtypes have tissue compartment-specific roles in mediating the effects of 17beta-estradiol on immune cell functions following trauma-hemorrhage.

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Section: Discussionsupporting

confidence: 92%

Tissue compartment-specific role of estrogen receptor subtypes in immune cell cytokine production following trauma-hemorrhage

Suzuki

Shimizu

et al. 2007

Journal of Applied Physiology

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“…Ex vivo exposure to GM-CSF has restored function in monocytes harvested from humans with septic shock (36) or from immunosuppressed liver transplant recipients (37). In a rat model of hemorrhagic shock, GM-CSF treatment in vivo has corrected tissue macrophage dysfunction (17). Our data are of particular interest because we have shown both that reduced local expression of GM-CSF is likely to account for AM dysfunction following sublethal hyperoxia and that treatment with GM-CSF largely corrects this defect.…”

Section: Discussionmentioning

confidence: 65%

GM-CSF and the impaired pulmonary innate immune response following hyperoxic stress

Baleeiro¹,

Christensen²,

Morris³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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We have previously demonstrated that mice exposed to sublethal hyperoxia (an atmosphere of Ͼ95% oxygen for 4 days, followed by return to room air) have significantly impaired pulmonary innate immune response. Alveolar macrophages (AM) from hyperoxia-exposed mice exhibit significantly diminished antimicrobial activity and markedly reduced production of inflammatory cytokines in response to stimulation with LPS compared with AM from control mice in normoxia. As a consequence of these defects, mice exposed to sublethal hyperoxia are more susceptible to lethal pneumonia with Klebsiella pneumoniae than control mice. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a growth factor produced by normal pulmonary alveolar epithelial cells that is critically involved in maintenance of normal AM function. We now report that sublethal hyperoxia in vivo leads to greatly reduced alveolar epithelial cell GM-CSF expression. Systemic treatment of mice with recombinant murine GM-CSF during hyperoxia exposure preserved AM function, as indicated by cell surface Toll-like receptor 4 expression and by inflammatory cytokine secretion following stimulation with LPS ex vivo. Treatment of hyperoxic mice with GM-CSF significantly reduced lung bacterial burden following intratracheal inoculation with K. pneumoniae, returning lung bacterial colony-forming units to the level of normoxic controls. These data point to a critical role for continuous GM-CSF activity in the lung in maintenance of normal AM function and demonstrate that lung injury due to hyperoxic stress results in significant impairment in pulmonary innate immunity through suppression of alveolar epithelial cell GM-CSF expression.

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“…In sepsis-associated immune dysfunction the administration of GM-CSF was able to counteract the reduced HLA-DR expression on monocytes as well as the reduced TNF-alpha producing capacity of whole blood cultures (Nierhaus et al, 2003). Concerning haemorrhagic shock, it has been demonstrated that GM-CSF given immediately after reperfusion could restore the diminished TNF-alpha response of spleen and peritoneal cells (Husain et al, 2004). When GM-CSF is given in vivo the restoration of the cytokine response may be explained by the generation of new macrophage populations from the bone marrow, which of course is activated by the haematopoietic growth factor GM-CSF.…”

Section: Shammentioning

confidence: 96%

“…GM-CSF is also reported to restore the reduced TNFalpha production of splenic and peritoneal macrophages after haemorrhagic shock in rats (Husain et al, 2004).…”

Section: Introductionmentioning

confidence: 97%

Haemorrhagic shock in mice – Intracellular signalling and immunomodulation of peritoneal macrophages’ LPS response

et al. 2006

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GM-CSF counteracts hemorrhage-induced suppression of cytokine-producing capacity

Abstract: Hemorrhagic shock caused a depression of the TNFalphaa response to LPS which was partly counteracted by treatment with GM-CSF. Therefore, GM-CSF represents a promising approach to normalise trauma- and shock-induced immune dysfunction.

Cited by 5 publications

References 40 publications

Tissue compartment-specific role of estrogen receptor subtypes in immune cell cytokine production following trauma-hemorrhage

Tissue compartment-specific role of estrogen receptor subtypes in immune cell cytokine production following trauma-hemorrhage

GM-CSF and the impaired pulmonary innate immune response following hyperoxic stress

Haemorrhagic shock in mice – Intracellular signalling and immunomodulation of peritoneal macrophages’ LPS response

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