**9. Anti-TNF-alpha in psoriasis and metabolic syndrome**

TNF-alpha is an inflammatory cytokine promoting inflammation via the activation and induction of proinflammatory cytokines (IL-1, IL-6, IL-8) and by the upregulation of adhesion molecules on endothelial cells leading to increased leukocyte extravasation (Channual J et al, 2009).

Given that TNF-a show a pivotal role in many inflammatory conditions and that it represents one of possible link between psoriasis and metabolic syndrome, theoretically the TNF-alpha blockade might have a widespread potential in the treatment of both pathological entities (Channual J et al, 2009).

Although it is well known the TNF-alpha inhibitors efficacy on PsO and Psoriatic arthritis (PsA), little is known about their effects on the MetS components in PsO patients.

Currently, three available in the United States are approved for psoriasis and psoriatic arthritis (PsA): infliximab, etanercept, and adalimumab (Channual J et al, 2009).

Infliximab is a chimeric monoclonal antibody binding the human tumor necrosis factor alpha (Staidle JP et al, 2011).

Actually there are no data in literature about infliximab effect on insulin resistance or sensitivity in PsO patients.

About lipid profiles, studies have shown that infliximab does not significantly modify total cholesterol, triglycerides and, interestingly, the patient's lipid profile reverted to baseline values after infliximab discontinuation (Gisondi P et al, 2008; Antoniou KM et al, 2008).

Studies investigating the effect of infliximab on body weight have reported significant increase in weight gain and in BMI, without differences among males and females (Saraceno R et al, 2009).

Etanercept is a fusion protein consisting of two molecules of extracellular domain of human p75 TNF-alpha receptor attached to the Fc domain of human immunoglobulin G1 (IgG1), that binds to TNF-alpha with greater affinity than natural receptor. The binding makes TNFalpha biologically inactive, with consequent reduction of inflammation (Weinberg JM, 2003).

Although there are conflicting results on the effect of Etanercept in insulin-resistance, etanercept have shown an interesting action on reducing serum insulin levels and improving insulin sensitivity. Similar to Infliximab, Etanercept does not significantly modify lipid profiles; furthermore, PsO patients treated by etanercept gradually and progressively gain weight, in particular lean ones (Marra M et al, 2007).

Adalimumab is human monoclonal antibody against TNF-alpha (Staidle JP et al, 2011).

Although there are no reports in literature discussing about adalimumab effect on insulin resistance or sensitivity in PsO patients, a recent case revealed episodes of hyperglycemia in a PsO-PsA patient; these increased serum glucose levels resolved after adalimumab discontinuation (Wu JJ et al, 2008).

Similar to Infliximab and Etanercept, Adalimumab does not modify lipid profiles and it increases BMI and weight gain (Saraceno R et al, 2009).
