Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM |
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Authors: | M J Hussain M Peakman H Gallati S S S Lo M Hawa G C Viberti P J Watkins R D G Leslie Professor D Vergani |
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Institution: | (1) Department of Immunology, King's College School of Medicine and Dentistry, Bessemer Road, SE5 9PJ London, UK;(2) Department of Medicine and Diabetes, King's College School of Medicine and Dentistry, London, UK;(3) Unit for Metabolic Medicine,United Medical and Dental Schools, Guy's Hospital, London, UK;(4) Department of Diabetes, St. Bartholomew's Hospital, London, UK;(5) F. Hoffmann-La Roche, Basel, Switzerland |
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Abstract: | 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- ), T helper 2 (interleukin-4 and inter-leukin-10) lymphocytes and macrophages (tumour necrosis factor- , interleukin-1 and interleukin-1 ) in patients before and after the onset of IDDM. Recently diagnosed IDDM patients had significantly higher levels of interleukin-2, interferon- , tumour necrosis factor- and interleukin-1 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- levels (p<0.01 for all). Interleukin-4 and interleukin-10 were detectable in sera of patients with Graves' disease only, while interleukin-1 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- and interleukin-1 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.Abbreviations IL
Interleukin
- IFN-
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-
tumour necrosis factor-alpha
- CTLL-16
murine cytotoxic cell line |
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Keywords: | Cytokines T helper subsets interleukin-2 interferon- " target="_blank">gif" alt="gamma" align="MIDDLE" BORDER="0"> interleukin-1 tumour necrosis factor prediabetes identical twins |
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