Affinity-purified Human Interleukin I is Cytotoxic to Isolated Islets of Langerhans

Overview

Journal Diabetologia

Specialty Endocrinology

Date 1986 Jan 1

PMID 3514344

Citations 79

Authors

T Mandrup-Poulsen

K Bendtzen

J Nerup

C A Dinarello

M Svenson

J H Nielsen

Affiliations

Soon will be listed here.

Abstract

Addition of highly purified human Interleukin-1 to the culture medium of isolated rat islets of Langerhans for 6 days led to 88% inhibition of glucose-induced insulin-release, reduction of islet contents of insulin and glucagon to 31% and 8% respectively, and disintegration of the islets. These effects were dose-dependent and reproducible when using three different Interleukin-1 preparations. Highly purified human Interleukin-2, Lymphotoxin, Leucocyte Migration Inhibitory Factor and Macrophage Migration Inhibitory Factor were ineffective. These findings suggest that Interleukin-1 may play an important role in the molecular mechanisms underlying autoimmune B-cell destruction leading to Type 1 (insulin-dependent) diabetes mellitus.

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References

Bendtzen K . Biological properties of interleukins. Allergy. 1983; 38(4):219-26. DOI: 10.1111/j.1398-9995.1983.tb01614.x. View

Mandrup-Poulsen T, Bendtzen K, Nielsen J, BENDIXEN G, Nerup J . Cytokines cause functional and structural damage to isolated islets of Langerhans. Allergy. 1985; 40(6):424-9. DOI: 10.1111/j.1398-9995.1985.tb02681.x. View

Rhodes C, Taylor K . Effect of human lymphoblastoid interferon on insulin synthesis and secretion in isolated human pancreatic islets. Diabetologia. 1984; 27(6):601-3. DOI: 10.1007/BF00276977. View

Nash J, Everson N, Wood R, Bell P . Effect of silica and carrageenan on the survival of islet allografts. Transplantation. 1980; 29(3):206-8. DOI: 10.1097/00007890-198003000-00008. View

DEBRAY-SACHS M, Boitard C, Assan R, Hamburger J . Are "activated" macrophages cytotoxic against normal cells?. Transplant Proc. 1981; 13(1 Pt 2):1111-3. View

Dinarello C, Renfer L, Wolff S . Human leukocytic pyrogen: purification and development of a radioimmunoassay. Proc Natl Acad Sci U S A. 1977; 74(10):4624-7. PMC: 431999. DOI: 10.1073/pnas.74.10.4624. View

Giulian D, Lachman L . Interleukin-1 stimulation of astroglial proliferation after brain injury. Science. 1985; 228(4698):497-9. DOI: 10.1126/science.3872478. View

Zier K, Leo M, Spielman R, Baker L . Decreased synthesis of interleukin-2 (IL-2) in insulin-dependent diabetes mellitus. Diabetes. 1984; 33(6):552-5. DOI: 10.2337/diab.33.6.552. View

Rocklin R, Bendtzen K, Greineder D . Mediators of immunity: lymphokines and monokines. Adv Immunol. 1980; 29:55-136. DOI: 10.1016/s0065-2776(08)60043-7. View

10.

Oschilewski U, Kiesel U, Kolb H . Administration of silica prevents diabetes in BB-rats. Diabetes. 1985; 34(2):197-9. DOI: 10.2337/diab.34.2.197. View

11.

Prudhomme G, Fuks A, Colle E, Seemayer T, Guttmann R . Immune dysfunction in diabetes-prone BB rats. Interleukin 2 production and other mitogen-induced responses are suppressed by activated macrophages. J Exp Med. 1984; 159(2):463-78. PMC: 2187220. DOI: 10.1084/jem.159.2.463. View

12.

Robb R, Kutny R, Chowdhry V . Purification and partial sequence analysis of human T-cell growth factor. Proc Natl Acad Sci U S A. 1983; 80(19):5990-4. PMC: 534345. DOI: 10.1073/pnas.80.19.5990. View

13.

Sibley R, Sutherland D, Goetz F, Michael A . Recurrent diabetes mellitus in the pancreas iso- and allograft. A light and electron microscopic and immunohistochemical analysis of four cases. Lab Invest. 1985; 53(2):132-44. View

14.

Heding L . Determination of total serum insulin (IRI) in insulin-treated diabetic patients. Diabetologia. 1972; 8(4):260-6. DOI: 10.1007/BF01225569. View

15.

Schwizer R, Leiter E, Evans R . Macrophage-mediated cytotoxicity against cultured pancreatic islet cells. Transplantation. 1984; 37(6):539-44. DOI: 10.1097/00007890-198406000-00002. View

16.

Brunstedt J . Rapid isolation of functionally intact pancreatic islets from mice and rats by percollTM gradient centrifucation. Diabete Metab. 1980; 6(2):87-9. View

17.

Virelizier J . Interferons as macrophage-activating factors. II. Enhanced secretion of interleukin 1 by lipopolysaccharide-stimulated human monocytes. Eur J Immunol. 1983; 13(6):437-40. DOI: 10.1002/eji.1830130602. View

18.

Bonner-Weir S, Orci L . New perspectives on the microvasculature of the islets of Langerhans in the rat. Diabetes. 1982; 31(10):883-9. DOI: 10.2337/diab.31.10.883. View

19.

Dinarello C . Interleukin-1 and the pathogenesis of the acute-phase response. N Engl J Med. 1984; 311(22):1413-8. DOI: 10.1056/NEJM198411293112205. View

20.

Auron P, Webb A, Rosenwasser L, Mucci S, Rich A, Wolff S . Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A. 1984; 81(24):7907-11. PMC: 392262. DOI: 10.1073/pnas.81.24.7907. View