Effects of IL-6 Signaling Pathway Inhibition on Weight and BMI: A Systematic Review and Meta-Analysis

Patsalos, Olivia; Dalton, Bethan; Himmerich, Hubertus

doi:10.3390/ijms21176290

Cited by 51 publications

(29 citation statements)

References 67 publications

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“…Altered concentrations of inflammatory markers may not only be of scientific interest as biomarkers or pivotal messenger molecules involved in the pathophysiology of AN. They may also represent future drug targets, because inhibitors of certain cytokine pathways are available and approved for the treatment of autoimmune disorders, and they have also been shown to influence weight in meta-analytic research [ 34 , 35 ]. Additional treatments such as non-steroidal anti-inflammatory drugs, omega-3 fatty acids, statins and minocyclines have shown anti-inflammatory effects in major depressive disorder [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Reduced MIP-1β as a Trait Marker and Reduced IL-7 and IL-12 as State Markers of Anorexia Nervosa

Keeler

Patsalos

Chung

et al. 2021

JPM

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Alterations in certain inflammatory markers have been found in individuals with anorexia nervosa (AN). However, their relation to clinical characteristics has not been extensively explored, nor is it clear whether they are trait or state features of the disorder. This cross-sectional study measured serum concentrations of 36 inflammatory markers in people with acute AN (n = 56), recovered AN (rec-AN; n = 24) and healthy controls (HC; n = 51). The relationship between body mass index (BMI), eating disorder psychopathology, depression symptoms and inflammatory markers was assessed. Statistical models controlled for variables known to influence cytokine concentrations (i.e., age, ethnicity, smoking status and medication usage). Overall, most inflammatory markers including pro-inflammatory cytokines were unchanged in AN and rec-AN. However, in AN and rec-AN, concentrations of macrophage inflammatory protein (MIP)-1β were lower than HCs. Interleukin (IL)-7 and IL-12/IL-23p40 were reduced in AN, and concentrations of macrophage-derived chemokine, MIP-1α and tumor necrosis factor-α were reduced in rec-AN compared to HC. In conclusion, a reduction in MIP-1β may be a trait marker of the illness, whereas reductions in IL-7 and IL-12/IL-23p40 may be state markers. The absence of increased pro-inflammatory cytokines in AN is contradictory to the wider literature, although the inclusion of covariates may explain our differing findings.

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Section: Introductionmentioning

confidence: 99%

Reduced MIP-1β as a Trait Marker and Reduced IL-7 and IL-12 as State Markers of Anorexia Nervosa

Keeler

Patsalos

Chung

et al. 2021

JPM

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“…It should be noted that whilst the LCV data supported strong partial genetic causality of CRP on AN, the MR evidence was less statistically significant, with some evidence in the MVMR that IL-6 signalling may exert a protective effect on AN conditioned-on CRP. Inhibition of the IL-6 pathway has been associated with weight gain which may be protective for AN (81). Furthermore, CRP likely is intertwined with other metabolic factors, including insulin signalling, which our group has previously shown through MR is also putatively protective for AN (48).…”

Section: Discussionmentioning

confidence: 99%

Genetic estimates of correlation and causality between blood-based biomarkers and psychiatric disorders

Kiltschewskij

Geaghan

Carr

et al. 2021

Preprint

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There is a long-standing interest in exploring the relationship between blood-based biomarkers of biological exposures and psychiatric disorders, despite their causal role being difficult to resolve in observational studies. In this study, we leverage genome-wide association study data for a large panel of heritable biochemical traits measured from serum to refine our understanding of causal effect in biochemical-psychiatric trait parings. In accordance with expectation we observed widespread evidence of positive and negative genetic correlation between psychiatric disorders and biochemical traits. We then implemented causal inference to distinguish causation from correlation and found strong evidence that C-reactive protein (CRP) exerts a causal effect on psychiatric disorders, along with other putatively causal relationships involving urate and glucose. Strikingly, these analyses suggested CRP has a protective effect on three disorders including anorexia nervosa, obsessive-compulsive disorder, and schizophrenia, whilst being a risk factor for major depressive disorder. Multivariable models that conditioned CRP effects on interleukin-6 signalling and body mass index suggested that CRP-schizophrenia relationship was not likely mediated by those factors. Collectively, these data suggest that there are shared pathways that influence both biochemical traits and psychiatric illness, including factors such as CRP that are likely to constitute a causal effect and could be targets for therapeutic intervention and precision medicine.

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“…Taken together, these findings suggest that elevated proinflammatory cytokines, and IL-6 in particular, may serve as state markers for AN. Moreover, a recent meta-analysis revealed that selective inhibition of the IL-6 signaling pathway is associated with an increase in weight gain [ 62 ]. This suggests that the IL-6 signaling pathway is involved in the regulation of body weight and could thus be targeted by available pharmacological IL-6 inhibitors to facilitate weight gain in AN patients.…”

Section: Anorexia Nervosa and Peripheral Inflammationmentioning

confidence: 99%

The Role of the Gut Microbiome, Immunity, and Neuroinflammation in the Pathophysiology of Eating Disorders

2021

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There is a growing recognition that both the gut microbiome and the immune system are involved in a number of psychiatric illnesses, including eating disorders. This should come as no surprise, given the important roles of diet composition, eating patterns, and daily caloric intake in modulating both biological systems. Here, we review the evidence that alterations in the gut microbiome and immune system may serve not only to maintain and exacerbate dysregulated eating behavior, characterized by caloric restriction in anorexia nervosa and binge eating in bulimia nervosa and binge eating disorder, but may also serve as biomarkers of increased risk for developing an eating disorder. We focus on studies examining gut dysbiosis, peripheral inflammation, and neuroinflammation in each of these eating disorders, and explore the available data from preclinical rodent models of anorexia and binge-like eating that may be useful in providing a better understanding of the biological mechanisms underlying eating disorders. Such knowledge is critical to developing novel, highly effective treatments for these often intractable and unremitting eating disorders.

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Effects of IL-6 Signaling Pathway Inhibition on Weight and BMI: A Systematic Review and Meta-Analysis

Cited by 51 publications

References 67 publications

Reduced MIP-1β as a Trait Marker and Reduced IL-7 and IL-12 as State Markers of Anorexia Nervosa

Reduced MIP-1β as a Trait Marker and Reduced IL-7 and IL-12 as State Markers of Anorexia Nervosa

Genetic estimates of correlation and causality between blood-based biomarkers and psychiatric disorders

The Role of the Gut Microbiome, Immunity, and Neuroinflammation in the Pathophysiology of Eating Disorders

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