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Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM

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Summary

To determine whether cytokines could have a role in the development of insulin-dependent diabetes mellitus (IDDM), we measured serum levels of cytokines derived from T helper 1 (interleukin-2 and interferon-γ), T helper 2 (interleukin-4 and inter-leukin-10) lymphocytes and macrophages (tumour necrosis factor-α, interleukin-1 α and interleukin-1 Β) in patients before and after the onset of IDDM. Recently diagnosed IDDM patients had significantly higher levels of interleukin-2, interferon-γ, tumour necrosis factor-α and interleukin-1 α than patients with either long-standing IDDM, non-insulin-dependent diabetes (NIDDM), Graves' disease, or control subjects (p<0.05 for all). Compared with control subjects, patients with long-standing IDDM and those with NIDDM had higher interleukin-2 and tumour necrosis factor-α levels (p<0.01 for all). Interleukin-4 and interleukin-10 were detectable in sera of patients with Graves' disease only, while interleukin-1 Β was not detectable in the serum of any control or test subject. To investigate whether high cytokine levels precede the onset of IDDM, we studied 28 non-diabetic identical co-twins of patients with IDDM, followed-up prospectively for up to 6 years after the diagnosis of the index. Levels of tumour necrosis factor-α and interleukin-1 α were elevated above the normal range more frequently in the eight twins who developed diabetes than in those 20 who did not (p<0.005). Analysis of T helper 1 and T helper 2 profiles of the twin groups did not reveal a clear difference between prediabetic twins and twins remaining non-diabetic. These results support the notion that T helper 1 lymphocytes may play a role in the development of IDDM. This is associated with release of macrophage-derived cytokines, which is also a feature of the prediabetic period. The lack of evidence of a dominant T helper 1 profile of cytokine release before diabetes onset suggests that additional events, activating this arm of the cellular immune response, are required in the immediate prediabetic period.

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Abbreviations

IL:

Interleukin

IFN-γ:

interferon-gamma

TH :

T helper

ICA:

islet-cell antibody

GAD:

glutamic acid decar-boxylase

IDDM:

insulin-dependent diabetes mellitus

NIDDM:

non-insulin-dependent diabetes mellitus

TNF-α:

tumour necrosis factor-alpha

CTLL-16:

murine cytotoxic cell line

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Authors and Affiliations

  1. Department of Immunology, King's College School of Medicine and Dentistry, Bessemer Road, SE5 9PJ, London, UK

    M. J. Hussain, M. Peakman &  D. Vergani

  2. Department of Medicine and Diabetes, King's College School of Medicine and Dentistry, London, UK

    P. J. Watkins

  3. Unit for Metabolic Medicine,United Medical and Dental Schools, Guy's Hospital, London, UK

    G. C. Viberti

  4. Department of Diabetes, St. Bartholomew's Hospital, London, UK

    S. S. S. Lo, M. Hawa & R. D. G. Leslie

  5. F. Hoffmann-La Roche, Basel, Switzerland

    H. Gallati

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  1. M. J. Hussain
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  2. M. Peakman
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  3. H. Gallati
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  4. S. S. S. Lo
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  8. R. D. G. Leslie
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  9. D. Vergani
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Hussain, M.J., Peakman, M., Gallati, H. et al. Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM. Diabetologia 39, 60–69 (1996). https://doi.org/10.1007/BF00400414

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  • DOI: https://doi.org/10.1007/BF00400414

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