Endangered Lymphocytes: The Effects of Alloxan and Streptozotocin on Immune Cells in Type 1 Induced Diabetes

Alloxan (ALX) and streptozotocin (STZ) are extensively used to induce type 1 diabetes (T1D) in animal models. This study is aimed at evaluating the differences in immune parameters caused by ALX and STZ. T1D was induced either with ALX or with STZ, and the animals were followed for up to 180 days. B...

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Main Authors: Luiz A. D. Queiroz, Josiane B. Assis, João P. T. Guimarães, Emanuella S. A. Sousa, Anália C. Milhomem, Karen K. S. Sunahara, Anderson Sá-Nunes, Joilson O. Martins
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2021/9940009
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author Luiz A. D. Queiroz
Josiane B. Assis
João P. T. Guimarães
Emanuella S. A. Sousa
Anália C. Milhomem
Karen K. S. Sunahara
Anderson Sá-Nunes
Joilson O. Martins
author_facet Luiz A. D. Queiroz
Josiane B. Assis
João P. T. Guimarães
Emanuella S. A. Sousa
Anália C. Milhomem
Karen K. S. Sunahara
Anderson Sá-Nunes
Joilson O. Martins
author_sort Luiz A. D. Queiroz
collection DOAJ
description Alloxan (ALX) and streptozotocin (STZ) are extensively used to induce type 1 diabetes (T1D) in animal models. This study is aimed at evaluating the differences in immune parameters caused by ALX and STZ. T1D was induced either with ALX or with STZ, and the animals were followed for up to 180 days. Both ALX and STZ induced a decrease in the total number of circulating leukocytes and lymphocytes, with an increase in granulocytes when compared to control mice (CT). STZ-treated mice also exhibited an increase in neutrophils and a reduction in the lymphocyte percentage in the bone marrow. In addition, while the STZ-treated group showed a decrease in total CD3+, CD4-CD8+, and CD4+CD8+ T lymphocytes in the thymus and CD19+ B lymphocytes in the pancreas and spleen, the ALX group showed an increase in CD4-CD8+ and CD19+ only in the thymus. Basal levels of splenic interleukin- (IL-) 1β and pancreatic IL-6 in the STZ group were decreased. Both diabetic groups showed atrophy of the thymic medulla and degeneration of pancreatic islets of Langerhans composed of inflammatory infiltration and hyperemia with vasodilation. ALX-treated mice showed a decrease in reticuloendothelial cells, enhanced lymphocyte/thymocyte cell death, and increased number of Hassall’s corpuscles. Reduced in vitro activation of splenic lymphocytes was found in the STZ-treated group. Furthermore, mice immunized with ovalbumin (OVA) showed a more intense antigen-specific paw edema response in the STZ-treated group, while production of anti-OVA IgG1 antibodies was similar in both groups. Thereby, important changes in immune cell parameters in vivo and in vitro were found at an early stage of T1D in the STZ-treated group, whereas alterations in the ALX-treated group were mostly found in the chronic phase of T1D, including increased mortality rates. These findings suggest that the effects of ALX and STZ influenced, at different times, lymphoid organs and their cell populations.
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spelling doaj-art-5d00fc9499494e20825973a5c61589ce2025-08-20T02:05:02ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/99400099940009Endangered Lymphocytes: The Effects of Alloxan and Streptozotocin on Immune Cells in Type 1 Induced DiabetesLuiz A. D. Queiroz0Josiane B. Assis1João P. T. Guimarães2Emanuella S. A. Sousa3Anália C. Milhomem4Karen K. S. Sunahara5Anderson Sá-Nunes6Joilson O. Martins7Laboratory of Immunoendocrinology, School of Pharmaceutical Sciences, Department of Clinical and Toxicological Analyses, University of São Paulo, São Paulo, SP, BrazilLaboratory of Experimental Immunology, Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, São Paulo, SP, BrazilLaboratory of Immunoendocrinology, School of Pharmaceutical Sciences, Department of Clinical and Toxicological Analyses, University of São Paulo, São Paulo, SP, BrazilLaboratory of Immunoendocrinology, School of Pharmaceutical Sciences, Department of Clinical and Toxicological Analyses, University of São Paulo, São Paulo, SP, BrazilInstitute of Tropical Pathology and Public Health, Department of Microbiology, Immunology, Parasitology and Pathology, Federal University of Goiás, Goiânia, GO, BrazilExperimental Physiopathology, Department of Sciences/Experimental Physiopathology, Medical School, University of São Paulo, São Paulo, SP, BrazilLaboratory of Experimental Immunology, Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, São Paulo, SP, BrazilLaboratory of Immunoendocrinology, School of Pharmaceutical Sciences, Department of Clinical and Toxicological Analyses, University of São Paulo, São Paulo, SP, BrazilAlloxan (ALX) and streptozotocin (STZ) are extensively used to induce type 1 diabetes (T1D) in animal models. This study is aimed at evaluating the differences in immune parameters caused by ALX and STZ. T1D was induced either with ALX or with STZ, and the animals were followed for up to 180 days. Both ALX and STZ induced a decrease in the total number of circulating leukocytes and lymphocytes, with an increase in granulocytes when compared to control mice (CT). STZ-treated mice also exhibited an increase in neutrophils and a reduction in the lymphocyte percentage in the bone marrow. In addition, while the STZ-treated group showed a decrease in total CD3+, CD4-CD8+, and CD4+CD8+ T lymphocytes in the thymus and CD19+ B lymphocytes in the pancreas and spleen, the ALX group showed an increase in CD4-CD8+ and CD19+ only in the thymus. Basal levels of splenic interleukin- (IL-) 1β and pancreatic IL-6 in the STZ group were decreased. Both diabetic groups showed atrophy of the thymic medulla and degeneration of pancreatic islets of Langerhans composed of inflammatory infiltration and hyperemia with vasodilation. ALX-treated mice showed a decrease in reticuloendothelial cells, enhanced lymphocyte/thymocyte cell death, and increased number of Hassall’s corpuscles. Reduced in vitro activation of splenic lymphocytes was found in the STZ-treated group. Furthermore, mice immunized with ovalbumin (OVA) showed a more intense antigen-specific paw edema response in the STZ-treated group, while production of anti-OVA IgG1 antibodies was similar in both groups. Thereby, important changes in immune cell parameters in vivo and in vitro were found at an early stage of T1D in the STZ-treated group, whereas alterations in the ALX-treated group were mostly found in the chronic phase of T1D, including increased mortality rates. These findings suggest that the effects of ALX and STZ influenced, at different times, lymphoid organs and their cell populations.http://dx.doi.org/10.1155/2021/9940009
spellingShingle Luiz A. D. Queiroz
Josiane B. Assis
João P. T. Guimarães
Emanuella S. A. Sousa
Anália C. Milhomem
Karen K. S. Sunahara
Anderson Sá-Nunes
Joilson O. Martins
Endangered Lymphocytes: The Effects of Alloxan and Streptozotocin on Immune Cells in Type 1 Induced Diabetes
Mediators of Inflammation
title Endangered Lymphocytes: The Effects of Alloxan and Streptozotocin on Immune Cells in Type 1 Induced Diabetes
title_full Endangered Lymphocytes: The Effects of Alloxan and Streptozotocin on Immune Cells in Type 1 Induced Diabetes
title_fullStr Endangered Lymphocytes: The Effects of Alloxan and Streptozotocin on Immune Cells in Type 1 Induced Diabetes
title_full_unstemmed Endangered Lymphocytes: The Effects of Alloxan and Streptozotocin on Immune Cells in Type 1 Induced Diabetes
title_short Endangered Lymphocytes: The Effects of Alloxan and Streptozotocin on Immune Cells in Type 1 Induced Diabetes
title_sort endangered lymphocytes the effects of alloxan and streptozotocin on immune cells in type 1 induced diabetes
url http://dx.doi.org/10.1155/2021/9940009
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