Glucocorticoid-Induced Impairment of Macrophage Antimicrobial Activity: Mechanisms and Dependence on the State of Activation

Schaffner, Andreas; Schaffner, Thomas

doi:10.1093/clinids/9.supplement_5.s620

Cited by 66 publications

(34 citation statements)

References 28 publications

(45 reference statements)

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“…Furthermore, it has been demonstrated that lymphokines, such as IFN-γ, can restore the microbicidal activity of glucocorticoid-suppressed macrophages [22]. Thus, it is conceivable that lymphocytes coexisting with PMs in the peritoneum could counterbalance the suppressive effect of Dex on the macrophages.…”

Section: Discussionmentioning

confidence: 99%

Effect of in vitro and in vivo administration of dexamethasone on rat macrophage functions: comparison between alveolar and peritoneal macrophages

Nakamura

Murai²,

Ogawa³

1996

Eur Respir J

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Resident alveolar macrophages (AMs) and peritoneal macrophages (PMs), though they originate from common precursor cells, differ morphologically and functionally. The two types of macrophages residing in different tissues may respond differently to glucocorticoids.In the present study, we compared the effects of a synthetic glucocorticoid, dexamethasone (Dex), on rat AMs and PMs with regard to their phagocytic activity and tumour necrosis factor-α (TNF-α) releasability.In vitro exposure of the macrophages to Dex caused the depression of phagocytic activity of AMs but not of PMs. In contrast, TNF-α releasability was depressed in the both types of macrophages, and no difference was found between AMs and PMs in their susceptibility to TNF-α regulation by Dex. When Dex was administered subcutaneously into rats, phagocytic activity was severely depressed in AMs but not in PMs. On the other hand, TNF-α releasability was depressed both in AMs and PMs by the in vivo Dex administration. The depression in PMs, however, was transitory and less severe than that in AMs.These results suggest that alveolar macrophages and peritoneal macrophages differ intrinsically in responses to glucocorticoid, and that the cell location and the cell's microenvironment can also modulate the effects of glucocorticoid on macrophage functions.

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Section: Discussionmentioning

confidence: 99%

Effect of in vitro and in vivo administration of dexamethasone on rat macrophage functions: comparison between alveolar and peritoneal macrophages

Nakamura

Murai²,

Ogawa³

1996

Eur Respir J

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“…Most studies have focused on the ability of stressors to suppress immunity, and it is now known that factors such as HPA axis-derived glucocorticoid (GC) hormones can suppress important transcription factors, such as NF-B (61). As a result, prolonged elevations of glucocorticoids have been shown to suppress macrophage activity (2,10,21,53).…”

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confidence: 99%

Stressor-Induced Increase in Microbicidal Activity of Splenic Macrophages Is Dependent upon Peroxynitrite Production

et al. 2012

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ABSTRACTExposing mice to a social stressor called social disruption (SDR) that involves repeated social defeat during intermale aggression results in increased circulating cytokines, such as interleukin-1α (IL-1α) and IL-1β, and increased reactivity of splenic CD11b+macrophages to inflammatory stimuli. For example, upon lipopolysaccharide stimulation, macrophages from stressor-exposed mice produce higher levels of cytokines than do cells from nonstressed controls. Moreover, the SDR stressor enhances the ability of these macrophages to killEscherichia colibothin vitroandin vivo, through a Toll-like receptor 4-dependent mechanism. The present study tested the hypothesis that stressor-enhanced bacterial killing is due to increases in the production of peroxynitrite. Male mice were exposed to the SDR stressor or were left undisturbed. Upon stimulation withE. coli, splenic macrophages from SDR-exposed mice expressed significantly increased levels of inducible nitric oxide synthase mRNA and produced higher levels of peroxynitrite. Blocking the production of peroxynitrite abrogated the SDR-induced increase in microbicidal activity. Studies in IL-1 receptor type 1 knockout mice indicated that the increased microbicidal activity and peroxynitrite production was dependent upon IL-1 signaling. These data confirm and extend the importance of IL-1 signaling for stressor-induced immunopotentiation; the finding that inhibiting superoxide or nitric oxide production inhibits both peroxynitrite production and killing ofE. colidemonstrates that peroxynitrite mediates the stressor-induced increase in bacterial killing.

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“…In vitro studies have demonstrated an inhibitory effect of high corticosteroid concentrations on oxygen radical production in human granulocytes [15]. In contrast, dexamethasone treatment has been reported to have no effect on ROS secretion in human blood-derived macrophages [16], but have a stimulatory effect on human monocytes [17]. It has been reported that in vivo corticosterone had no effect on murine peritoneal inflammatory cells [18].…”

mentioning

confidence: 99%

Superoxide anion production by monocytes of corticosteroid-treated asthmatic patients

Majori

Vachier²,

Godard³

et al. 1998

Eur Respir J

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Bronchial asthma is a chronic inflammatory disease of the airways characterized by an increased recruitment of inflammatory cells, including mononuclear phagocytic cells such as monocytes [1]. The ability of these cells to generate highly reactive oxygen species (ROS), including super-oxide anion, following activation of a membraneassociated reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important part of the host defence system, and has also been implicated in inflammation in a variety of pulmonary diseases [2,3], including asthma [4,5]. Oxygen metabolites cause tissue injury, smooth muscle contraction, increased airway vascular permeability, and may increase airway responsiveness and release of var-ious mediators [4].In previous studies, it has been shown that alveolar macrophages [6], blood monocytes [5] and eosinophils [7] from asthmatic patients were able to produce high amounts of ROS. Alveolar macrophage activation was correlated with the severity of asthma [6]. This activation occurred immediately after antigen challenge, and the appearance of high-density macrophages which release higher amounts of superoxide anion occurred during the late airway response [8]. Several investigators have also suggested that polymorphonuclear leucocytes from asthmatic patients generated more ROS than control subjects [9,10]. This activation was correlated with the level of bronchial hyperreactivity [11].Corticosteroids are the most potent anti-inflammatory agents available for the treatment of asthma [12], but little is known about their molecular mechanism of action in improving symptoms or the way they reduce hyperresponsiveness. It has been proposed that corticosteroids inhibit the inflammatory process by redirection of lymphocyte traffic, inhibition of cytokine gene expression [13] and inhibition of the expression of adhesion molecules [14].The effect of anti-inflammatory corticosteroids on oxygen radical production by phagocytes has been less extensively studied, and the results are contradictory. In vitro studies have demonstrated an inhibitory effect of high corticosteroid concentrations on oxygen radical production in human granulocytes [15]. In contrast, dexamethasone treatment has been reported to have no effect on ROS secretion in human blood-derived macrophages [16], but have a stimulatory effect on human monocytes [17]. It has been reported that in vivo corticosterone had no effect on murine peritoneal inflammatory cells [18]. Ex vivo inhaled steroid treatment had no effect on superoxide anion production in human alveolar macrophages [19,20]. In contrast, a recent study showed that in vivo administration of dexamethasone or methylprednisolone led to a dose-dependent inhibition of rat peritoneal leucocyte chemiluminescence [21]. Moreover, hydrocortisone was found to inhibit superoxide anion production during an asthma attack [22].Superoxide anion production by monocytes of corticosteroid-treated asthmatic patients. M. Majori, I. Vachier, P. Godard, M. Farce, J. Bousquet, P. Chanez. ...

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Glucocorticoid-Induced Impairment of Macrophage Antimicrobial Activity: Mechanisms and Dependence on the State of Activation

Cited by 66 publications

References 28 publications

Effect of in vitro and in vivo administration of dexamethasone on rat macrophage functions: comparison between alveolar and peritoneal macrophages

Effect of in vitro and in vivo administration of dexamethasone on rat macrophage functions: comparison between alveolar and peritoneal macrophages

Stressor-Induced Increase in Microbicidal Activity of Splenic Macrophages Is Dependent upon Peroxynitrite Production

Superoxide anion production by monocytes of corticosteroid-treated asthmatic patients

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