Cytokine concentrations in people with eating disorders: A comprehensive updated systematic review and meta-analysis

Prior research has found altered levels of cytokines in people with eating disorders (EDs). This study is an update of a previous meta-analysis, including longitudinal analyses and machine learning heterogeneity analyses (MetaForest).

This pre-registered ( https://osf.io/g6d3f ) systematic review and meta-analysis following PRISMA guidelines assessed studies from four databases (PubMed, Web of Science, MEDLINE, PsycINFO) reporting cytokine concentrations in people with EDs until 10^th November 2024. Random-effects models were utilised for all meta-analyses.

Twenty-four new studies are incorporated, resulting in a total of 43 studies included in meta-analyses. Interleukin (IL)-6 and IL-15 are higher, and IL-7 lower, in anorexia nervosa (AN) compared with controls. When controlling for outliers, tumour necrosis factor (TNF)-α, IL-1β, IL-4, IL-8, IL-10, interferon (IFN)-γ, monocyte chemoattractant protein (MCP) and transforming growth factor (TGF)-β are similar between AN and controls. Longitudinally, IL-6 is lower in AN at follow-up compared to baseline, although this may be an artefact of publication bias. TNF-α and IL-1β do not change longitudinally. There are largely no differences in IL-6 and TNF-α in bulimia nervosa (BN) and there are insufficient studies to perform meta-analyses for binge eating disorder or other EDs.

In acute AN, concentrations of IL-6 and IL-15 are elevated and IL-7 is decreased, with preliminary but unconclusive evidence for small decreases in IL-6 over the course of weight restoration. Other cytokines considered to have broadly pro-inflammatory functions are not increased in AN. In BN, there is little evidence for increases in pro-inflammatory cytokines, but the evidence base is limited.