Lise Wogensen

Mechanisms of pancreatic beta-cell destruction in type I diabetes

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • J Nerup
  • ,
  • T Mandrup-Poulsen
  • ,
  • J Mølvig
  • ,
  • S Helqvist
  • ,
  • L Wogensen
  • J Egeberg, Danmark

The pathogenetic mechanisms leading to beta-cell destruction and insulin-dependent diabetes mellitus (IDDM) are major histocompatibility complex (MHC) nonrestricted and are MHC associated and beta-cell specific. The macrophage peptide hormone interleukin 1 (IL-1) may be the primary MHC-nonrestricted beta-cell-destructive molecule. Beta-Cell death most likely results from free radical induction by IL-1. Thus, islet cell-specific antibodies and cytotoxic T-lymphocytes are secondary in importance and time. The potentiation of IL-1 effects on beta-cells by tumor necrosis factor alpha (TNF), another macrophage hormone controlled by a gene in the HLA region on chromosome 6, may account for the MHC association of IDDM. In the experimental model of IDDM etiopathogenesis described, release of beta-cell antigen, processed and presented by macrophages to helper T-lymphocytes, initiates a self-perpetuating and self-limiting circuit of cytokine production of which IL-1 is beta-cell cytotoxic. As postulated, the IL-1 effect is potentiated by TNF, whereas IL-1 and/or TNF production is controlled in a quantitative way by HLA-D genes.

OriginalsprogEngelsk
TidsskriftDiabetes Care
Vol/bind11
NummerSuppl 1
Sider (fra-til)16-23
Antal sider8
ISSN0149-5992
StatusUdgivet - 1 nov. 1988

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