Targeting cytokines in the 5-Lox pro-inflammatory pathway for treatment-resistant anorexia nervosa

Abstract

Cytokines are a class of pro-inflammatory immune responses in the peripheral and central nervous system. Elevated cytokine levels contribute to appetite and weight dysregulation, anxiety, depression and other psychiatric conditions, and may underlie eating disorder (ED). Recently, two meta-analyses of cytokine levels in people with EDs – particularly anorexia nervosa (AN) – confirm elevated levels of cytokines within the 5-LOX inflammatory pathway, namely interleukin 1 (IL-1), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α). IL-1, IL-6 and TNF-α are leukotrienes that stimulate the prolonged response of nuclear factor kappa beta (NF-κβ) – the major inflammatory gateway molecule – which influences brain development and function within the hypothalamicpituitary- adrenal (HPA) axis, hippocampus and prefrontal cortex. The structure and function of these brain areas are shown to be aberrant in neuroimaging studies of EDs; thus, neuroinflammatory processes are significant biomarkers for weight and cognitive disturbances in EDs, particularly AN. Against this background, this brief article summarises the current knowledge of IL-1, IL-6 and TNF-α in EDs. Thereafter, the significance of inhibiting the NF-κβ 5-LOX inflammatory pathway with a low-risk, Cochrane-reviewed, anti-inflammatory known as Boswellia serrata is considered. Brief discussion of the clinical role for Boswellia serrata in weight recovery and reduction of comorbid mental disorder in ED is provided to stimulate further research into natural anti-inflammatory treatment interventions.