Demonstration of a TH1cytokine profile in the late phase of NOD insulitis
| Autor: | Lars Björk, Jan Böhme, Björn Pilström |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Aging
medicine.medical_specialty Time Factors medicine.medical_treatment Immunology Fluorescent Antibody Technique Stimulation Nod Biology Biochemistry Lesion Interferon-gamma Islets of Langerhans Mice chemistry.chemical_compound Mice Inbred NOD Internal medicine medicine Animals Immunology and Allergy Molecular Biology Cells Cultured NOD mice Interleukin-6 Tumor Necrosis Factor-alpha Ionomycin Granulocyte-Macrophage Colony-Stimulating Factor Pancreatic Diseases Hematology medicine.disease Interleukin-10 Diabetes Mellitus Type 1 Endocrinology Cytokine Microscopy Fluorescence chemistry Cytokines Interleukin-2 Tetradecanoylphorbol Acetate Female Tumor necrosis factor alpha Interleukin-4 medicine.symptom Insulitis Interleukin-1 |
| Zdroj: | Cytokine. 7:806-814 |
| ISSN: | 1043-4666 |
| DOI: | 10.1006/cyto.1995.0097 |
| Popis: | Cells infiltrating the Langerhans' islets of prediabetic NOD females were isolated from 6 weeks to 6 months of age. These cells were assayed at a single-cell level for production of eight different cytokines by intracellular immunofluorescent staining. By in vitro stimulation with PMA and ionomycin for 4 hours the method is enhanced also to detect in vivo preactivated cells. During the early phase of insulitis from 6 to 12 weeks of age, mainly the monokines IL-1 alpha, IL-6, and TNF were detected. After stimulation, also IFN-gamma and low numbers of IL-10 and GM-CSF producing cells could be observed, but no IL-2 or IL-4 was seen. This cytokine pattern correlates with an increasing insulitis, and we suggest that these cytokines are important in attracting inflammatory cells to the islets, and may cause initial beta-cell destruction. During a later phase, between 4 and 6 months, there is a characteristic TH1 cytokine profile with production of IL-2 and IFN-gamma occurring after stimulation, as well as lymphocytes producing TNF, supposedly TNF-beta. During this period IL-10 was very rarely observed, and no IL-4 production could be found throughout the study. This indicates the absence of a TH2 cytokine profile in this lesion. In addition IL-6 production occurs in high frequencies at all ages, also in endocrine islet cells. We interpret this as a stress response caused by the inflammatory lesion. Our findings show that the effector phase in NOD insulitis is TH1 rather than TH2 mediated. We also demonstrate that cytokines, that may cause initial tissue destruction, are produced during the recruitment of inflammatory cells. |
| Databáze: | OpenAIRE |
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