New insights into the resolution of inflammation

Gilroy, Derek W.; Maeyer, Roel P.H. De

doi:10.1016/j.smim.2015.05.003

Cited by 113 publications

(70 citation statements)

References 89 publications

(63 reference statements)

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“…Previous reports have shown GC-induced upregulation of CCR2 on human monocytes in vitro 47 or following exercise-induced increases in circulating cortisol 48 . Notably, monocytes expressing high levels of CCR2 are the monocyte subpopulation that initiates the dynamic process of inflammation and subsequent wound repair 49,50 . Similar results have been reported for CXCR4 expression and migratory responses of human T lymphocytes 51 .…”

Section: Discussionmentioning

confidence: 99%

“…Although we do not know if the migrated macrophages that we observed in the sterile chamber fluid came directly from the peripheral circulation or whether or they were present in the surrounding cellular matrix, the coincidental finding of monocytopenia suggests that at least some of these cells entered from peripheral blood. Once at an inflammatory site, monocytes differentiate into macrophages that manifest a wide array of regulatory processes to coordinate an ongoing inflammatory process, including its eventual resolution 49,50 . There is increasing evidence that the latter process is accompanied by ‘activation switching’ in which macrophages convert from a largely pro-inflammatory phenotype to a more anti-inflammatory phenotype 49,62–65 .…”

Section: Discussionmentioning

confidence: 99%

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Glucocorticoids enhance the in vivo migratory response of human monocytes

Yeager

Pioli

Collins

et al. 2016

Brain, Behavior, and Immunity

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Glucocorticoids (GCs) are best known for their potent anti-inflammatory effects. However, an emerging model for glucocorticoid (GC) regulation of in vivo inflammation also includes a delayed, preparatory effect that manifests as enhanced inflammation following exposure to an inflammatory stimulus. When GCs are transiently elevated in vivo following exposure to a stressful event, this model proposes that a subsequent period of increased inflammatory responsiveness is adaptive because it enhances resistance to a subsequent stressor. In the present study, we examined the migratory response of human monocytes/macrophages following transient in vivo exposure to stress-associated concentrations of cortisol. Participants were administered cortisol for 6 hours to elevate in vivo cortisol levels to approximate those observed during major systemic stress. Monocytes in peripheral blood and macrophages in sterile inflammatory tissue (skin blisters) were studied before and after exposure to cortisol or placebo. We found that exposure to cortisol induced transient upregulation of monocyte mRNA for CCR2, the receptor for monocyte chemotactic protein-1 (MCP-1/CCL2) as well as for the chemokine receptor CX3CR1. At the same time, mRNA for the transcription factor IκBα was decreased. Monocyte surface expression of CCR2 but not CX3CR1 increased in the first 24 hours after cortisol exposure. Transient exposure to cortisol also led to an increased number of macrophages and neutrophils in fluid derived from a sterile inflammatory site in vivo. These findings suggest that the delayed, pro-inflammatory effects of cortisol on the human inflammatory responses may include enhanced localization of effector cells at sites of in vivo inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Glucocorticoids enhance the in vivo migratory response of human monocytes

Yeager

Pioli

Collins

et al. 2016

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

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“…A life-threatening condition responsible for ~250,000 U.S. deaths annually, sepsis can occur when a localized infection fails to properly resolve, leading to systemic inflammation, organ failure and death (2, 3, 9). In humans and mice, sepsis is associated with widespread apoptosis in lymphoid organs causing dramatic reductions in hematopoietic cell numbers, including thymic T cells, bone marrow B cells and peripheral lymphocytes (7, 10).…”

Section: Introductionmentioning

confidence: 99%

Efferocytosis Signaling in the Regulation of Macrophage Inflammatory Responses

Elliott

Koster

Murphy

2017

The Journal of Immunology

323

274

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Since the pioneering work of Elie Metchnikoff and the discovery of cellular immunity, the phagocytic clearance of cellular debris has been considered an integral component of resolving inflammation and restoring function of damaged and infected tissues. We now know that the phagocytic clearance of dying cells (efferocytosis), particularly by macrophages and other immune phagocytes, has profound consequences on innate and adaptive immune responses in inflamed tissues. These immunomodulatory effects result from an array of molecular signaling events between macrophages, dying cells and other tissue-resident cells. In recent years, many of these molecular pathways have been identified and studied in the context of tissue inflammation, helping us better understand the relationship between efferocytosis and inflammation. We review specific types of efferocytosis-related signals that can impact macrophage immune responses and discuss their relevance to inflammation-related diseases.

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“…Here, we will primarily focus on lung infection and inflammation. The resolution responses that occur in non- pulmonary sites of infection and inflammation have recently been reviewed (see REFS 7,19–21). Finally, we consider how new therapeutic strategies that incorporate immunoresolvents may have the potential to synergize with antibiotics and to mitigate the growing problem of antibiotic resistance.…”

mentioning

confidence: 99%

Specialized pro-resolving mediators: endogenous regulators of infection and inflammation

2015

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Specialized pro-resolving mediators (SPMs) are enzymatically derived from essential fatty acids and have important roles in orchestrating the resolution of tissue inflammation -that is, catabasis. Host responses to tissue infection elicit acute inflammation in an attempt to control invading pathogens. SPMs are lipid mediators that are part of a larger family of pro-resolving molecules, which includes proteins and gases, that together restrain inflammation and resolve the infection. These immunoresolvents are distinct from immunosuppressive molecules as they not only dampen inflammation but also promote host defence. Here, we focus primarily on SPMs and their roles in lung infection and inflammation to illustrate the potent actions these mediators play in restoring tissue homeostasis after an infection.Acute inflammation is a vital response to infection that is initiated within seconds of pathogen detection 1 . Granulocytes are rapidly recruited to sites of infection 2 , where they become activated and augment the resident capacity of infected tissue to kill and ultimately clear the pathogen 3 . These early events in the host response to infection are essential for survival and are coordinated by several families of pro-inflammatory mediators, including lipid mediators (such as prostaglandins and leukotrienes), cytokines and chemokines. These pro-inflammatory mediators have overlapping and distinct functions and ultimately induce an increase in vascular permeability and orchestrate leukocyte recruitment. This leads to the cardinal signs of tissue inflammation -namely calor, rubor, tumor, dolor and potentially functio laesa (FIG. 1).Recently, a new array of molecules that function in the resolution of inflammation were elucidated and named specialized pro-resolving mediators (SPMs) 4,5 . Many of these SPMs are produced during the acute inflammatory response 6 , and their structure, biosynthesis and organic synthesis have been recently reviewed (see REF. 5). Typically, acute inflammatory responses to pathogens are self-limiting, and there is a growing appreciation that SPMs have pivotal anti-inflammatory and anti-infective roles in tissue catabasis 4 . For effective Correspondence to B.D.L. blevy@partners.org. Competing interests statementThe authors declare competing interests: see Web version for details. DATABASES ClinicalTrials.gov: http://www.clinicaltrials.gov ALL LINKS ARE ACTIVE IN THE ONLINE PDF HHS Public AccessAuthor manuscript Nat Rev Immunol. Author manuscript; available in PMC 2017 January 18. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript resolution of inflammation to occur in tissues, cessation of granulocyte recruitment is required in conjunction with the recruitment and differentiation of macrophages, which help clear inflammatory cells and tissue debris to restore tissue homeostasis 7 . Granulocytes in the tissue undergo apoptosis during the resolution of inflammation to prevent bystander tissue injury occurring from the release of potentially toxic cellular conten...

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New insights into the resolution of inflammation

Cited by 113 publications

References 89 publications

Glucocorticoids enhance the in vivo migratory response of human monocytes

Glucocorticoids enhance the in vivo migratory response of human monocytes

Efferocytosis Signaling in the Regulation of Macrophage Inflammatory Responses

Specialized pro-resolving mediators: endogenous regulators of infection and inflammation

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