title: Molecular mechanisms of action of anti-TNF-α agents - Comparison among therapeutic TNF-α antagonists.
abstract: Tumor necrosis factor (TNF)-α is a potent pro-inflammatory and pathological cytokines in inflammatory diseases such as rheumatoid arthritis and inflammatory bowel diseases. Anti-TNF-α therapy has been established as an efficacious therapeutic strategy in these diseases. In clinical settings, three monoclonal anti-TNF-α full IgG1 antibodies infliximab, adalimumab, and golimumab, PEGylated Fab' fragment of anti-TNF-α antibody certolizumab pegol, extracellular domain of TNF receptor 2/IgG1-Fc fusion protein etanercept, are almost equally effective for rheumatoid arthritis. Although monoclonal full IgG1 antibodies are able to induce clinical and endoscopic remission in inflammatory bowel diseases, certolizumab pegol without Fc portion has been shown to be less effective for inflammatory bowel diseases compared to full IgG1 antibodies. In addition, there are no evidences that etanercept leads clinical remission in inflammatory bowel diseases. Besides the common effect of anti-TNF-α agents on neutralization of soluble TNF-α, each anti-TNF-α agent has its own distinctive pharmacological properties which cause the difference in clinical efficacies. Here we focus on the distinctions of action of anti-TNF-α agents especially in following points; (1) blocking ability against ligands, transmembrane TNF-α and lymphotoxin, (2) effects toward transmembrane TNF-α-expressing cells, (3) effects toward Fcγ receptor-expressing cells, (4) degradation and distribution in inflamed tissue. Accumulating evidence will give us the idea how to modify anti-TNF-α agents to enhance the clinical efficacy in inflammatory diseases.
authors: Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital, Fukuoka 812-8582, Japan. Electronic address: mitoma@intmed1.med.kyushu-u.ac.jp.
authors: Hiroki
authors: H
authors: Mitoma
authors: Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu 874-0838, Japan.
authors: Takahiko
authors: T
authors: Horiuchi
authors: Department of Internal Medicine, Shin-Kokura Hospital, Kitakyushu 803-8505, Japan.
authors: Hiroshi
authors: H
authors: Tsukamoto
authors: Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital, Miyazaki 880-8510, Japan.
authors: Naoyasu
authors: N
authors: Ueda
mesh_terms: D000068879:Adalimumab / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D000068582:Certolizumab Pegol / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use; D004195:Disease Models, Animal; D000068800:Etanercept / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D000069285:Infliximab / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use; D051379:Mice; D011092:Polyethylene Glycols / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; C529000:golimumab; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D000068582:Certolizumab Pegol
keywords: Anti-TNF-α therapy; Inflammatory bowel disease; Rheumatoid arthritis; Tumor necrosis factor-α