Nerup J, Mandrup-Poulsen T, Mølvig J, Helqvist S, Wogensen L, Egeberg J
Steno Memorial Hospital, Gentofte, Denmark.
Diabetes Care. 1988 Nov-Dec;11 Suppl 1:16-23.
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.
导致β细胞破坏和胰岛素依赖型糖尿病（IDDM）的发病机制主要是非主要组织相容性复合体（MHC）限制的，且与MHC相关并具有β细胞特异性。巨噬细胞肽激素白细胞介素1（IL-1）可能是主要的非MHC限制的β细胞破坏分子。β细胞死亡很可能是由IL-1诱导自由基所致。因此，胰岛细胞特异性抗体和细胞毒性T淋巴细胞在重要性和时间上是次要的。肿瘤坏死因子α（TNF）是另一种由6号染色体上HLA区域的一个基因控制的巨噬细胞激素，它对IL-1作用于β细胞的增强作用，可能解释了IDDM与MHC的关联。在所描述的IDDM发病机制的实验模型中，β细胞抗原的释放由巨噬细胞处理并呈递给辅助性T淋巴细胞，启动了一个自我持续和自我限制的细胞因子产生回路，其中IL-1具有β细胞细胞毒性。正如所假设的，TNF增强了IL-1的作用，而IL-1和/或TNF的产生则由HLA-D基因以定量方式控制。
