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Researchers discover peptide that may reduce rheumatoid arthritis

BMJ 2001; 322 doi: (Published 05 May 2001) Cite this as: BMJ 2001;322:1084
  1. Xavier Bosch
  1. Barcelona

    Patients with rheumatoid arthritis might soon benefit from a treatment based on an endogenously occurring natural peptide known as vasoactive intestinal peptide.

    A team of researchers led by Mario Delgado from the faculty of biology of the Complutense University of Madrid reported this month in Nature Medicine (2001;7:563-8) that administration of the peptide in mice with a rheumatoid arthritis-like disease strikingly suppressed clinical joint disease. It also seemed to block both the inflammatory and autoimmune components inherent in the disorder.

    By immunising mice with type II collagen, the researchers induced a type of arthritis that shares some clinical, histological, and immunological features with rheumatoid arthritis. They administered the peptide intraperitoneally at different doses.

    Compared with untreated arthritic mice, those given the peptide had delayed onset, lower incidence, and decreased severity of arthritis depending on the dose. Histological analyses of joints showed a complete abrogation of chronic inflammation, cartilage damage, and bone erosion.

    Further studies showed that the peptide also increased anti-inflammatory cytokines as well as an inhibiting proinflammatory cytokines.

    In fact, arthritis induced by collagen is an example of an autoimmune disease mediated by proinflammatory cytokines. Mice treated with the peptide also showed a significantly lower proliferative response of synovial cells to type II collagen compared with control mice with arthritis. In addition, the peptide suppressed production of a subset of matrix metalloproteinases (protein degrading enzymes, secreted by fibroblasts and tissue cells, which digest extracellular matrix) believed to contribute to joint destruction in paws of arthritic mice.

    Dr Delgado said that because the peptide regulates the two components of the disease and modulates several inflammatory mediators it offers an advantage over some current approaches to the treatment of rheumatoid arthritis, such as neutralising antibodies or antagonists against a unique cytokine.

    “Since we are convinced of the potential therapeutic role of the peptide in patients with rheumatoid arthritis, we intend to start clinical trials as soon as possible,” he said.

    But in an accompanying article in the same issue of Nature Medicine (pp 537-8) Gary Firestein from the division of rheumatology at the University of California at San Diego's School of Medicine in La Jolla cautioned that “chronic administration of a neuropeptide such as vasoactive intestinal peptide might have detrimental gastrointestinal effects or lead to dysregulation of host defense.”

    However, he added: “Although direct treatment with [anti-inflammatory] cytokines is a reasonable approach, administration of vasoactive intestinal peptide may be superior, reshaping both the immune and inflammatory responses.”

    Dr Delgado said that because this was a natural peptide, it “may avoid undesirable side effects.” He believes there is also the possibility of using genetic therapy through inducing the local synthesis of the peptide in the affected joint, thereby avoiding its systemic administration.

    View Abstract

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