Dysfunctional serotoninergic regulation and hypothalamic–pituitary–adrenal (HPA) axis overreactivity have been consistently reported in research studies with eating disorders (ED). In addition, the links between stress response, serotonin function, HPA axis and inflammatory mechanisms in ED have also been suggested in a number of studies. In our study, inflammatory parameters in white blood cells were investigated in 26 female patients with ED and 25 healthy control subjects matched for sex, age and ethnicity. Patients were free of medication for at least two weeks at the time of the study. Results showed a significant increase in plasma levels of the proinflammatory cytokine IL1β and the protein expression of cyclooxygenase 2 (COX2) in peripheral mononuclear blood cells (PMBCs) in ED patients compared with controls. As well as a significant increase of the oxidative-nitrosative marker TBARS (Thiobarbituric Acid Reactive Substances) in plasma. These findings were associated with increased expression of the alpha7 subunit of the nicotinic receptor (α7nAChR) in PMBC in ED patients independent of plasma cotinine levels.
These results suggest that a pro-inflammatory and oxidant phenotype might be present in ED patients. Further research on cellular inflammatory and anti-inflammatory pathways might be oriented to investigate differences between ED subtypes and to search for new potential targets for pharmacological treatment.
DSM-IV criteria for Anorexia Nervosa (AN) include inadequate weight lost, an intense fear of gaining weight or becoming fat, a refusal to maintain normal weight for age and height, and amenorrhea. Binge-eating or purging behavior is present in the Binge Eating/Purging type but not in the restrictive type of AN. Bulimia Nervosa (BN) is characterized for recurrent episodes of binge eating and inappropriate compensatory behavior such as fasting, purging or exercise. Finally Eating disorder not otherwise specified (ED-NOS) might be described as an eating disorder that does not meet the criteria for AN or BN (American Psychiatric Association, 2000).
Etiopathogenesis of eating disorders is still not fully known, and data about possible biomarkers are scarce. Alterations in some neurotransmitters have been proposed (Crisp, 1978 and Leibowitz, 1987) as well as genetic abnormalities (Scherag et al., 2010). Among neurochemical research studies on ED patients, dysfunctional serotoninergic regulation (Ribases et al., 2008) and hypothalamic–pituitary–adrenal (HPA) axis overreactivity (Basurte et al., 2004 and Bruce et al., 2012) are the most consistently reported findings. Furthermore, the linkage between stress response, inflammation factors and anorexia nervosa has been proposed in several studies with eating disorders (Silva, 2011 and Brambilla, 2001). Stress related sympathetic nervous system activation releases catecholamines, which in turn enhances production of proinflammatory mediators such as cytokines Tumor Necrosis Factor Alpha (TNFα) or Interleukin 1 beta (IL1β), nuclear transcription factors such as kappa B (NFκB) and Nitric Oxide (NO) ( Lucas et al., 2006). These inflammatory and oxido-nitrosative mediators have been shown to be increased in brain and at peripheral level, in both animal ( García-Bueno et al., 2008) and human models of stress ( Bierhaus et al., 2003).
A number of studies have examined the inflammatory response in patients with eating disorders suggesting that significant changes at the cytokine levels are present in these patients. Elevated concentrations of TNF-α, IL-6 (Ahren-Moonga et al., 2011, Brambilla et al., 1998, Emeric Sauval et al., 1989, Kahl et al., 2004, Mitchel et al., 1994, Nakai et al., 1999 and Pomeroy et al., 1994;) and IL-1β (Nova et al., 2002) have been reported. Some authors have proposed a “cytokine hypothesis” for ED based on the presentation of symptomatic anorexia following inflammatory conditions or fever syndromes (Corcos et al., 2003 and Dantzer, 2004). However, other studies have reported negative findings in eating disorders (Brambilla, 2001, Monteleone et al., 1999, Polack et al., 1993, Schattner et al., 1990a and Schattner et al., 1990b).
Regulation of inflammation includes both inflammatory and anti-inflammatory processes. Two major anti-inflammatory mechanisms are: (1) cyclopentenone prostaglandins derived from the differential activation of cyclooxygenase (COX) isoforms by different physio-pathological stimuli, and (2) the activation of the alpha7 subunit of the nicotinic receptor (α7nAChR), which has been implicated in controlling the NFκB-mediated inflammatory mechanisms (Altavilla et al., 2006).
Based on data obtained in experimental stress models and in clinical studies in patients with eating disorders (Corcos et al., 2003, Nova et al., 2002 and Raymond et al., 2000) we have tested the hypothesis of a disruption of the physiological equilibrium of proinflammatory/anti-inflammatory pathways in ED. Particullarly, we have explored a group of intracellular and soluble components of inflammatory and oxidative response in patients and healthy controls.
