Anti-TNF-α Antibody Therapies in Autoimmune Diseases

Abstract

Autoimmune diseases affect about 3% of the world population, more frequently women than men, and their incidence is attributed to an immune response of a genetically predisposed individual to an environmental pathogen, under the influence of inadequate immuno-regulatory mechanisms. Advances in understanding the cellular activity pathways and cytokine expression profiles have led to new therapeutic regiments, like soluble receptors, monoclonal antibodies and molecular mimetics that have been employed to enhance or replace conventional immunosuppressive therapies. Among new biologicals that have been developed to target defined pathways of the adaptive immune response are TNF-alpha inhibitors. TNF-alpha is a proinflammatory cytokine elevated in many autoimmune lesions, and its deregulation characterizes many autoimmune diseases. TNF-alpha seems to exhibit an immunoregulatory role that can alter the balance of T regulatory cells and orchestrate acute immunological responses. More than half a million autoimmune patients have received therapy with anti-TNF-alpha antibodies, usually because they were refractory to conventional treatments. This review offers an update on TNF-alpha-targeted therapies used in patients suffering from various autoimmune diseases, based on the current knowledge of disease pathogenesis, with emphasis on the efficacy and safety that clinical trials have shown until now.

TNF α: A Trigger of Autonomic Dysfunction

“…There is a strong correlation between pathological states that demonstrate gastric stasis, nausea, and emesis that also are associated with elevated, circulating TNF α levels (e.g., Beattie and others 2002;Chatzantoni and Mouzaki 2006;Hermann, Holmes, and Rogers 2005;Kasner and others 2001;Kurzrock 2001;Muller and Meineke 2007;Stoll, Jander, and Schroeter 2002;Turrin and Plata-Salaman 2000). These observations lead to the hypothesis that TNF α might act on the neural circuits that control gastrointestinal function.…”

“…A number of noninfectious pathophysiological processes including autoimmune disorders (Chatzantoni and Mouzaki 2006), metastatic carcinoma (Kurzrock 2001), trauma (Beattie and others 2002), ischemia (Stoll, Jander, and Schroeter 2002), and radiation exposure (Muller and Meineke 2007) are also associated with elevated levels of TNF α . These disease processes are strongly associated with delayed digestive processes, visceral malaise, nausea, and emesis (e.g., Hermann, Holmes, and Rogers 2005;Kasner and others 2001;Turrin and Plata-Salaman 2000).…”

Inhibition of Tumour Necrosis Factor (Tnf) Activity by a New Ergostane Steroid From Cleome Droserifolia

“…Its overproduction leads to the development of chronic autoimmune diseases. Its role seems to be immune-regulatory that can change the balance of T regulatory cells and regulate acute immunological responses [5]. Inhibition of TNF production or function by small molecules has become a major focus in the pharmaceutical industry for the treatment of rheumatoid arthritis.…”

“…However, advances in understanding the cellular activity pathways have led to new therapeutic treatments targeting defined pathways of the adaptive immune response such as tumour necrosis factor-alpha inhibitors (TNF-α) [5].…”

“…The UV spectrum (λmax 350 nm in MeOH) revealed that it possessed a conjugated triene structure composed of Δ [5,6] and Δ [7,9], with an extra conjugated double bond which could be located in either position Δ 9( [11] ) or Δ [14,15]. Comparing its spectral data with dehydroergosterol (DHE) and 14-DHE revealed that the position of the additional double bond was suggested to be located at C-9 as in dehydroergosterol.…”