Treatment of anorexia nervosa with TNF-α down-regulating agents

Abstract

Patients suffering from anorexia nervosa present a certain level of immune system activation that is either considered a cause of this eating disorder or an accompanying feature of the malnutrition state (1). Cytokines deregulation profile in these patients includes an increase in interleukine 1-Beta (IL-1β) and in tumor necrosis factor-alpha (TNF-α) levels and a downregulation of interferon-gamma (INF-ψ). Accordingly, it has been hypothesized that anorexia nervosa may result from a genetically transmitted insufficiency in producing neutralizing antibodies to TNF-α and/or IL-1β (2). In addition, organic diseases in which we can find an elevated TNF-α such is the case in rheumatoid arthritis, ankylosing spondylarthritis and Crohn’s disease — are often accompanied by anorexia and cachexia (3). Many TNF-α downregulating agents are currently available. These are naloxone, pentoxifylline, dexamethasone, infliximab, etanercept, adalimumab, golimumab, certolizumab pegol, bupropion, fusidic acid, pentamidine, R-phenylisopropyladenosine, chlorpromazine, magnesium supplements etc. (3). Studies showed that the experimental use of TNF-α down-regulator, naloxone, in the treatment of anorexia nervosa is successful. It directly inhibits TNF-α production which reactivates lipid synthesis and reverses insulin resistance. It will also enhance weight gain and increase beta-endorphins and interleukin-4 (IL-4) which will further down-regulate TNF-α (3). In a case report, a woman suffering from an active juvenile idiopathic arthritis (despite methotrexate treatment) and simultaneously anorexia nervosa presented an improvement in her mood symptoms and in her appetite, two weeks after a treatment with infliximab. An 8% increase over her pretreatment weight was noticed after 5 months of treating her with this anti TNF-α agent (4). Other direct TNF-α down-regulating agents such as infliximab, etanercept, golimumab and certolizumab have not been evaluated so far as a treatment of anorexia nervosa although there is a strong theoretical rationale that could justify such an assessment. Accordingly, randomized controlled trials evaluating the efficiency of TNF-α down-regulating agents in patients suffering from anorexia nervosa are needed in this domain.