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 38 publications

(23 citation statements)

References 66 publications

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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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Section: Discussionmentioning

confidence: 99%

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

Kiltschewskij

Geaghan

Carr

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Importantly, it has been surmised that AN may result from an inability to produce neutralizing antibodies to TNF-a and/or IL-1b (37). Direct TNFa, IL-1b, and IL-6 down-regulating monoclonal antibodies such as infliximab, adalimumab, etanercept, and tocilizumab as well as monoclonal antibodies against appetite-regulating hormones have not been evaluated as a treatment of AN and BN so far, although there is a strong theoretical rationale that could justify such a study (38,39). Beneficial effects of anti-TNF-a therapy and an improvement in psychopathological traits in a case of AN with comorbid Crohn's disease and with juvenile idiopathic arthritis were reported (40,41).…”

Section: Involvement Of Autoimmunity In An and Bn Pathogenesismentioning

confidence: 99%

Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders

et al. 2021

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The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.

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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 38 publications

References 66 publications

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

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

Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders

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

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