ENDOGENOUS TNF PRODUCTION DIFFERS BETWEEN HIGH AND LOW DIABETES INCIDENCE NONOBESE DIABETIC (NOD) MICE

被引：7

作者：

CHOSICH, N ^{[1
]}

ROCKETT, E ^{[1
]}

HARRISON, LC ^{[1
]}

机构：

[1] ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,BURNET CLIN RES UNIT,PARKVILLE,VIC 3050,AUSTRALIA

来源：

AUTOIMMUNITY | 1994年 / 18卷 / 03期

关键词：

INSULIN-DEPENDENT DIABETES MELLITUS (IDDM); NOD MOUSE; TUMOR NECROSIS FACTOR (TNF); SYNGENEIC MIXED LYMPHOCYTE REACTION (SMLR);

D O I：

10.3109/08916939409007992

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Tumour necrosis factor (TNF) has been implicated in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). To investigate a possible role for TNF in IDDM we compared endogenous TNF production in two lines of non-obese diabetic (NOD) mice, NOD/Lt and NOD/WEHI, that have a high and low incidence of diabetes, respectively. Preliminary experiments had shown that the lower syngeneic mixed lymphocyte reaction (SMLR) in NOD/Lt mice could be corrected by TNF-alpha. Plasma TNF-alpha was measured in 8 week-old female non-diabetic mice primed with 1000 units IV of murine interferon gamma (IFN-gamma) followed after 3 hours by 5 mu g IV of lipopolysaccharide (LPS). Two hours later plasma was collected and TNF measured by ELISA. Plasma TNF in NOD/Lt mice was 9.2 +/- 2.4 ng/ml (mean +/- SEM, n = 16) compared to 2.5 +/- 0.5 ng/ml in NOD/WEHI mice (n = 15) and 7.6 +/- 1.0 ng/ml in BALB/c mice (n = 14). Time course studies demonstrated higher levels of both immunoreactive and bioactive TNF in NOD/Lt compared to NOD/WEHI mice up to 4 hours post-stimulation. A separate group of female NOD/Lt mice had IFN-gamma/LPS-stimulated plasma TNF-alpha measured at 10 weeks and were followed to age 30 weeks. The mean stimulated plasma TNF-alpha level was consistently higher in those mice that developed diabetes compared to those that remained non-diabetic, the difference being significant when mice were 21 weeks of age. These results suggest that endogenous TNF-alpha production may be a trait marker of IDDM susceptibility.

引用

页码：163 / 168

页数：6

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