Binding immunoglobulin protein resolves rheumatoid synovitis: a xenogeneic study using rheumatoid arthritis synovial membrane transplants in SCID mice

IntroductionBinding immunoglobulin protein (BiP) has previously shown powerful anti-inflammatory properties in the collagen-induced arthritis (CIA) model, where a single dose of BiP has proved to be both a long-term prophylactic and therapeutic. In both CIA and human in vitro studies, BiP induced regulatory T cells. The present investigation looked at the anti-inflammatory effect of BiP on inflamed human synovial tissue transplanted into severe combined immunodeficient mice (SCID), a chimaeric in vivo model previously used to test the efficacy of biologic therapies.MethodsRheumatoid arthritis synovial membrane (RASM) was engrafted into SCID mice. Following successful engraftment, mice were intravenously injected with BiP or human serum albumin in the presence or absence of anti-IL-10 mAb. Twelve days later the grafts were removed for analysis and human cytokines in the sera were quantified by ELISA. The extent of residual inflammatory cellular infiltrate in the synovial explants was determined by weight of the explants.ResultsThe RASM transplants from mice treated with BiP showed visual reduction in cellular infiltrate and downregulation of all quantifiable features of inflammation as assessed by the Koizumi or Rooney histological criteria. Also downregulated were HLA-DR, CD86, IL-6 and TNFα expression as assessed by immunohistology. ELISA detected significantly less human IL-6 circulating in the BiP-treated mouse serum. After removal of transplanted tissue 12 days post administration of BiP, the RASM explants from the BiP-treated SCID mice weighed significantly less, indicating a suppression of tissue inflammation. Mice given concomitant neutralising anti-IL-10 antibody and BiP showed no such suppression.ConclusionsBiP has anti-inflammatory properties partially dependent on the downregulation of HLA-DR and co-stimulatory molecules and the predominant production of IL-10.

• Publication year

  2011

• Venue

  Arthritis Research & Therapy

• Publication date

  2011-09-14

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/ar3463PMID 21914218PMCID 3308077
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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