Increased in vivo production of tumor necrosis factor after development of diabetes in nontreated, long-term diabetic BB rats

Shun ichi Tanaka, Hiroaki Seino, Jo Satoh, Noriyuki Fujii, Hidemi Rikiishi, Xiao Ping Zhu, Kazuma Takahashi, Mikio Sagara, Toshima Nobunaga, Takayoshi Toyota

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Abstract

We have recently reported that chronic and systemic administration of tumor necrosis factor α (TNF) inhibits development of autoimmune diabetes in NOD mice and BB rats, animal models of insulin-dependent diabetes mellitus (IDDM). During these experiments, we unexpectedly found that in vivo production of TNF stimulated by a single injection of lipopolysaccharide was enhanced approximately 10 times in the long-term diabetic BB rats (P < 0.0001), whose mean duration of diabetes with more than 16.8 mM (300 mg/dl) of nonfasting blood glucose level was 26.2 ± 2.1 days, as compared to that in the rats of nondiabetes and in the rats at the onset of diabetes, whose mean duration of diabetes was 1.4 ± 0.6 days. The long-term diabetic, but not short-term-diabetic, rats were also associated with increased levels of serum fructosamine/albumin (P < 0.01) and triglyceride (P < 0.01) and with a decreased level of serum albumin (P < 0.01). The in vivo TNF productivity in the diabetic rats, including the short-term- and long-term-diabetic rats, was correlated positively with the level of fructosamine/albumin (P < 0.05) and negatively with the level of serum albumin (P < 0.05), but not with levels of blood glucose. None of these correlations were observed in nondiabetic rats. The increased LPS-induced serum TNF activity in the long-term diabetic state was observed not only in BB rats but also in NOD mice and GK rats, a model of non-IDDM, irrespective of sexes and ages, indicating that the enhancement of in vivo TNF production was a result of long-term diabetes. These findings indicate that some factor(s) associated with the long-term-diabetic state may prime macrophages in vivo to produce TNF. Further study is needed to reveal a mechanism of the enhanced TNF production and its possible relevance to various abnormalities associated with the chronic hyperglycemic state.

Original languageEnglish
Pages (from-to)258-263
Number of pages6
JournalClinical Immunology and Immunopathology
Volume62
Issue number3
DOIs
Publication statusPublished - 1992 Mar

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology

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    Tanaka, S. I., Seino, H., Satoh, J., Fujii, N., Rikiishi, H., Zhu, X. P., Takahashi, K., Sagara, M., Nobunaga, T., & Toyota, T. (1992). Increased in vivo production of tumor necrosis factor after development of diabetes in nontreated, long-term diabetic BB rats. Clinical Immunology and Immunopathology, 62(3), 258-263. https://doi.org/10.1016/0090-1229(92)90100-3