ContextChronic systemic inflammation in obesity originates from local immune responses in visceral adipose tissue. However, assessment of a broad range of inflammation-mediating cytokines and their relationship to physical activity and adipometrics has scarcely been reported to date.ObjectiveTo characterize the profile of a broad range of pro- and anti-inflammatory cytokines and the impact of physical activity and energy expenditure in individuals with general obesity, central obesity, and non-obese subjects.Design, Setting, and ParticipantsA cross-sectional study comprising 117 obese patients (body mass index (BMI) ≥ 30) and 83 non-obese community-based volunteers.Main Outcomes MeasuresSerum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured. Physical activity and energy expenditure (MET) were assessed with actigraphy. Adipometrics comprised BMI, weight, abdominal-, waist- and hip-circumference, waist to hip ratio (WHR), and waist-to-height-ratio (WHtR).ResultsGeneral obesity was associated with significantly elevated levels of IL-5, IL-10, IL-12, IL-13, IFN-γ and TNF-α, central obesity with significantly elevated IL-5, IL-10, IL-12, IL-13 and IFN-γ-levels. In participants with general obesity, levels of IL-4, IL-10 and IL-13 were significantly elevated in participants with low physical activity, even when controlled for BMI which was negatively associated with physical acitivity. Cytokines significantly correlated with adipometrics, particularly in obese participants.ConclusionsResults confirm up-regulation of certain pro- and anti-inflammatory cytokines in obesity. In obese subjects, physical activity may lower levels and thus reduce pro-inflammatory effects of cytokines that may link obesity, insulin resistance and diabetes.

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Cytokines have been implicated in the pathology of depression. Currently, the evidence is based on cross-sectional studies and meta-analytic research comparing blood concentrations of T helper type 1 (TH1), T helper type 2 (TH2), pro-inflammatory or anti-inflammatory cytokines of patients with a depressive disorder to those of healthy controls. Additionally, multiple longitudinal studies have investigated cytokine levels during antidepressant treatment. According to the current literature, it seems that peripheral levels of interleukin (IL)-6, IL-10, IL-12, IL-13, and tumor necrosis factor (TNF)-α are elevated and that interferon (IFN)-γ levels are lower in patients with depression compared to healthy controls. However, the overlap of cytokine values between acutely depressed patients, remitted and recovered patients and healthy controls is considerable. Thus, the discriminative power of cytokine concentrations between depressed and non-depressed people is likely weak. Treatment with certain antidepressants appears to decrease peripheral levels of IL-6, IL-10, and TNF-α. However, weight gain-inducing psychopharmacological substances, such as the antidepressant mirtazapine, have been reported to potentially increase the production of pro-inflammatory cytokines. Even though cytokines are often discussed as biomarkers for depression, they have also been shown to be altered in other psychiatric disorders. Moreover, many environmental, social, psychological, biological, and medical factors are also associated with cytokine changes. Thus, cytokine alterations seem extremely unspecific. The interpretation of the results of these studies remains a challenge because it is unknown which type of cells are most responsible for cytokine changes measured in the blood nor have the main target cells or target tissues been identified. The same cytokine can be produced by multiple cell types, and the same cell can produce various cytokines. Additionally, redundancy, synergy, antagonism, and signaling cascades of cytokine signaling must be considered. Cytokines might not be associated with the diagnosis of depression according to the currently used diagnostic manuals, but rather with specific subtypes of depression, or with depressive symptoms across different psychiatric diagnoses. Therefore, the currently available diagnostic systems may not be the ideal starting point for psychiatric cytokine research.

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been shown to promote slow-wave sleep (SWS, non-REM sleep stages 3 and 4). Plasma levels of ghrelin are dependent on food intake and increase in sleeping subjects during the early part of the night. It is unknown whether sleep itself affects ghrelin levels or whether circadian networks are involved. Therefore, we studied the effect of sleep deprivation on nocturnal ghrelin secretion. In healthy male volunteers, plasma levels of ghrelin, cortisol, and human growth hormone (hGH) were measured during two experimental sessions of 24 h each: once when the subjects were allowed to sleep between 2300 and 0700 and once when they were kept awake throughout the night. During sleep, ghrelin levels increased during the early part of the night and decreased in the morning. This nocturnal increase was blunted during sleep deprivation, and ghrelin levels increased only slightly until the early morning. Ghrelin secretion during the first hours of sleep correlated positively with peak hGH concentrations. We conclude that the nocturnal increase in ghrelin levels is more likely to be caused by sleep-associated processes than by circadian influences. During the first hours of sleep, ghrelin might promote sleep-associated hGH secretion and contribute to the promotion of SWS.

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Cytokines are signalling molecules, which play an important role in both immune system function and brain development and function, and subsequently mental states and behaviour. Cytokines have been implicated in eating disorders (EDs) due to their role in psychological health, body weight and appetite regulation. This meta-analysis examined cross-sectional and longitudinal studies measuring concentrations of cytokines in individuals with EDs. Using PRISMA guidelines, we systematically reviewed relevant articles in PubMed, Web of Science, and MEDLINE. Random-effects meta-analyses were conducted for interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β, and tumor necrosis factor (TNF)-α, independently, firstly with all EDs combined and then stratified by ED diagnosis. Twenty-five studies were included: serum/plasma cytokine concentrations were measured in people with anorexia nervosa (AN) in 23 studies and bulimia nervosa (BN) in 4 studies. TNF-α and IL-6 were elevated in ED participants compared to healthy controls (HCs). Specifically, this pattern was seen only when comparing AN participants to HCs. Concentrations of these cytokines did not differ between people with BN and HCs. IL-1β and TGF-β did not differ between HCs and any ED group. Therefore, AN seems to be associated with elevated concentrations of TNF-α and IL-6. Considering the role of cytokines in appetite, mood regulation, and anxiety, these pro-inflammatory cytokines could be a potential future drug target to help people with AN, not only with weight gain, but also with various coexisting psychological problems. Future studies should consider confounding factors that affect cytokine concentrations and report ED-relevant clinical characteristics.