Systemic bias of cytokine production toward cell-mediated immune regulation in IDDM and toward humoral immunity in Graves' disease
| Autor: | Joachim Feldkamp, Hubert Kolb, Monika Tubes, Lampeter Ef, F. A. Gries, B. A. Kallmann, Manfred Hüther, J. Bertrams |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Adult
Male endocrine system medicine.medical_specialty Cellular immunity endocrine system diseases Adolescent medicine.medical_treatment Graves' disease Endocrinology Diabetes and Metabolism Autoantigens Sex Factors Th2 Cells Immunity Internal medicine Immunopathology HLA-DQ Antigens medicine Internal Medicine Humans Insulin Receptor-Like Protein Tyrosine Phosphatases Class 8 Child Autoantibodies Autoimmune disease Protein Tyrosine Phosphatase Non-Receptor Type 1 Immunity Cellular biology business.industry Glutamate Decarboxylase Membrane Proteins Middle Aged Th1 Cells medicine.disease Graves Disease Cytokine Endocrinology Diabetes Mellitus Type 1 Immunology Humoral immunity biology.protein Cytokines Female Antibody Protein Tyrosine Phosphatases business |
| Zdroj: | Diabetes. 46:237-243 |
| ISSN: | 0012-1797 |
| DOI: | 10.2337/diabetes.46.2.237 |
| Popis: | Disturbed immune regulation has been postulated to be crucial in the pathogenesis of IDDM and other autoimmune or allergic diseases. We therefore tested the hypothesis of a general bias in the peripheral immune system in patients with recent-onset IDDM or Graves' disease in comparison to healthy control subjects by studying whole blood cultures stimulated with phytohemagglutinin. Cells from IDDM patients (n = 53) produced significantly higher amounts of Th1 cytokines gamma-interferon (IFN-gamma) (P = 0.028) and tumor necrosis factor alpha (TNF-alpha) (P = 0.007) than normal control subjects (n = 56), while Th2 cytokine levels (interleukin [IL]-4, IL-10) were similar. Low levels of islet cell antibodies (ICAs) in IDDM patients were associated with high levels of Th1 and Th2 cytokines. Antibodies to GAD, ICA512, or insulin did not correlate with individual cytokine profiles. Also, HLA-DQ types did not significantly correlate with either Th1 or Th2 cytokine production. Conversely, whole blood cultures from patients with Graves' disease (n = 18) produced significantly less TNF-alpha and IL-4 than normal subjects (P = 0.001-0.006). However, when the balance between Th1 and Th2 cytokine production was analyzed in individuals, the ratio between IFN-gamma or TNF-alpha and IL-4 or IL-10 was clearly biased toward Th1 reactivity in patients with IDDM (P = 0.0001), while a dominance of Th2 cytokine production was seen in Graves' disease (P = 0.0001). The ratio of counterregulatory cytokines appeared to be the most reliable marker of the individual disease process. This study provides first evidence of a systemic bias in the immune regulation of humans, which might be either toward cell-mediated immunity (Th1) in IDDM or humoral immunity (Th2) in Graves' disease. |
| Databáze: | OpenAIRE |
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