Can we induce tolerance in rheumatoid arthritis?
Oral tolerance (OT) has worked well in numerous laboratory animal models of autoimmune diseases. Humans have been orally tolerized to keyhole limpet hemocyanin (KLH); patients with systemic sclerosis (SSc, scleroderma) have been orally tolerized to oral type I collagen (CI). However, clinical trials of oral type II collagen (CII) therapy in rheumatoid arthritis (RA) have had mixed results. Clinical studies show that compounds (such as nonsteroidal antiinflammatory drugs and prednisone) that inhibit generation of PGE(2) block OT induction. In murine OT models, the PGE(1) analog, misoprostol, reverses the NSAID OT block. These animal studies suggest that OT to CII or other antigens in patients with RA should be inducible if measures are taken to maintain normal prostaglandin function in the gut- associated lymphoid tissue (GALT). A clinical trial is underway in patients with RA to assess whether withholding NSAIDs and prednisone will allow OT to to be induced, and whether oral CII has meaningful clinical efficacy in this disease.
Postlethwaite
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Department of Medicine, Division of Connective Tissue Diseases, University of Tennessee Memphis, and Department of Veterans Affairs Medical Center, 956 Court Ave, Room G 326, Memphis, TN 38163, USA. apostlethwai@utmem.edu
D000020:Abortifacient Agents, Nonsteroidal / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D002986:Clinical Trials as Topic; D003094:Collagen / Q000627:therapeutic use; D004361:Drug Tolerance / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology; D016595:Misoprostol / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D016896:Treatment Outcome
D000020:Abortifacient Agents, Nonsteroidal; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D016595:Misoprostol; D003094:Collagen; D011241:Prednisone