Tumor necrosis factor-alpha (
TNF-alpha) is a central regulator of
inflammation, and
TNF-alpha antagonists may be effective in treating inflammatory disorders in which
TNF-alpha plays an important pathogenetic role. Recombinant or modified
proteins are an emerging class of therapeutic agents. To date, several recombinant or modified
proteins which acts as
TNF antagonists have been disclosed. In particular,
antibodies that bind to and neutralise TNF have been sought as a means to inhibit TNF activity. Inhibition of TNF has proven to be an effective
therapy for patients with
rheumatoid arthritis and other forms of inflammatory disease including
psoriasis,
psoriatic arthritis, and
ankylosing spondylitis,
inflammatory bowel disease. Additionally, the efficacy of preventing
septic shock and
AIDS has been questioned as a result of recent research. The currently available
therapies include a soluble p75
TNF receptor:Fc construct,
etanercept, a chimeric
monoclonal antibody,
infliximab, and a fully human
monoclonal antibody,
adalimumab.
Certolizumab pegol is a novel
TNF inhibitor which is an
antigen-binding domain of a humanized TNF antibody coupled to
polyethylene glycol (PEG) to increase half-life, and thus is Fc-domain-free. In this review, we discuss briefly the present understanding of
TNF-alpha-mediated biology and the current
therapies in clinical use, and focus on some of the new therapeutic approaches with small-molecule inhibitors. Moreover, we examine recent reports providing important insights into the understanding of efficacy of
thalidomide and its analogs, as
TNF-alpha activity inhibitories, especially in
therapies of several inflammatory diseases within the nervous system.