Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation

Rummel, Christoph; Inoue, Wataru; Poole, Stephen; Luheshi, Giamal N.

doi:10.1038/mp.2009.98

Cited by 76 publications

(85 citation statements)

References 64 publications

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“…Consistent with this, recent data highlight increased inflammatory processes in the brain of obese individuals (Buckman et al, 2013;Rummel et al, 2010). This is particularly notable in the hypothalamus, where clinical indication of glial activation has been reported (Thaler et al, 2012).…”

Section: Is Inflammation Linking Fat To Depression?supporting

confidence: 70%

Role of Adiposity-Driven Inflammation in Depressive Morbidity

Capuron

Lasselin

Castanon

2016

Neuropsychopharmacol

141

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Depression and metabolic disorders, including overweight and obesity, appear tightly interrelated. The prevalence of these conditions is concurrently growing worldwide, and both depression and overweight/obesity represent substantial risk factors for multiple medical complications. Moreover, there is now multiple evidence for a bidirectional relationship between depression and increased adiposity, with overweight/obesity being associated with an increased prevalence of depression, and in turn, depression augmenting the risk of weight gain and obesity. Although the reasons for this intricate link between depression and increased adiposity remain unclear, converging clinical and preclinical evidence points to a critical role for inflammatory processes and related alterations of brain functions. In support of this notion, increased adiposity leads to a chronic low-grade activation of inflammatory processes, which have been shown elsewhere to have a potent role in the pathophysiology of depression. It is therefore highly possible that adiposity-driven inflammation contributes to the development of depressive disorders and their growing prevalence worldwide. This review will present recent evidence in support of this hypothesis and will discuss the underlying mechanisms and potential therapeutic targets. Altogether, findings presented here should help to better understand the mechanisms linking adiposity to depression and facilitate the identification of new preventive and/or therapeutic strategies.

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Section: Is Inflammation Linking Fat To Depression?supporting

confidence: 70%

Role of Adiposity-Driven Inflammation in Depressive Morbidity

Capuron

Lasselin

Castanon

2016

Neuropsychopharmacol

141

View full text Add to dashboard Cite

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“…For instance, these antibodies are reported also to detect neutrophil granulocytes (Matsumoto et al, 2007;Saito et al, 1991;Wu et al, 2003). However, with the dose of LPS (100 lg/kg) at the time points investigated, neutrophils should be hardly detectable in the brain, as previously shown in a time-course experiment in mice (Rummel et al, 2009), and CD68/CD163-positive cells did not show a segmented nuclear DAPI stain that is characteristic for neutrophils. In addition, Dijkstra et al (1985) and Graeber et al (1989) reported that perivascular cells are as well detected by the antibody raised against CD68 that stains activated microglia although with a much weaker staining intensity.…”

Section: Nf-il6 Ir Cell Phenotypesmentioning

confidence: 67%

Spatiotemporal nuclear factor interleukin‐6 expression in the rat brain during lipopolysaccharide‐induced fever is linked to sustained hypothalamic inflammatory target gene induction

Damm

Luheshi

Gerstberger

et al. 2010

J of Comparative Neurology

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Rats injected with lipopolysaccharide (LPS) show brain-controlled sickness symptoms, including fever. In these animals, early genomic activation of brain cells was previously monitored by immunohistochemical detection of transcription factors such as nuclear factor (NF)-κB or signal transducer and activator of transcription (STAT)3 and was linked to the initiation or maintenance of the febrile response. To investigate whether NF-IL6 might be another important transcription factor implicated in this kind of immune-to-brain signaling, rats were injected with LPS (100 μg/kg, intraperitoneally) or phosphate-buffered saline, and brains were analyzed by immunohistochemistry, real-time PCR, or Western blot 4, 6, 8, and 10 hours later. Moderate to strong LPS-induced nuclear NF-IL6 immunoreactivity (IR) occurred in a time-dependent manner within circumventricular organs, namely, the vascular organ of the lamina terminalis, the subfornical organ, the area postrema, and the median eminence, brain structures with a leaky blood-brain barrier. Furthermore, nuclear NF-IL6-IR was observed in the pituitary gland, the choroid plexus, and the meninges as well as blood vessels throughout the entire brain. Endothelial, microglial, and ependymal cells, astrocytes, perivascular macrophages, and neurons exhibited LPS-induced nuclear NF-IL6-IR; mRNA levels of NF-IL6, responsive inflammatory genes, and NF-IL6 protein levels were significantly elevated. As opposed to observations on STAT3 or NFκB, the percentage of NF-IL6-reactive cells increased in parallel to late phases of the febrile response. In conclusion, these results suggest a potential role for NF-IL6 in the maintenance or possibly the termination of LPS-induced fever. Moreover, we propose NF-IL6 to be a delayed brain cell activation marker.

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“…Moreover, systemic inflammation, such as that found in our patients, has been invoked as a mechanism for neuroinflammation in other neurodegenerative disease models (47)(48)(49). In animal models, systemic administration of LPS alone has been shown to result in neuroinflammation (45,50).…”

Section: Discussionmentioning

confidence: 99%

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Montoya

Holmes

Anderson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

312

265

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Although some signs of inflammation have been reported previously in patients with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), the data are limited and contradictory. High-throughput methods now allow us to interrogate the human immune system for multiple markers of inflammation at a scale that was not previously possible. To determine whether a signature of serum cytokines could be associated with ME/CFS and correlated with disease severity and fatigue duration, cytokines of 192 ME/CFS patients and 392 healthy controls were measured using a 51-multiplex array on a Luminex system. Each cytokine’s preprocessed data were regressed on ME/CFS severity plus covariates for age, sex, race, and an assay property of newly discovered importance: nonspecific binding. On average, TGF-β was elevated (P = 0.0052) and resistin was lower (P = 0.0052) in patients compared with controls. Seventeen cytokines had a statistically significant upward linear trend that correlated with ME/CFS severity: CCL11 (Eotaxin-1), CXCL1 (GROα), CXCL10 (IP-10), IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α. Of the 17 cytokines that correlated with severity, 13 are proinflammatory, likely contributing to many of the symptoms experienced by patients and establishing a strong immune system component of the disease. Only CXCL9 (MIG) inversely correlated with fatigue duration.

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Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation

Cited by 76 publications

References 64 publications

Role of Adiposity-Driven Inflammation in Depressive Morbidity

Role of Adiposity-Driven Inflammation in Depressive Morbidity

Spatiotemporal nuclear factor interleukin‐6 expression in the rat brain during lipopolysaccharide‐induced fever is linked to sustained hypothalamic inflammatory target gene induction

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

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