An early but intense cytokine production within the islets may be predictive for type 1 diabetes occurrence in the Bio Breeding (BB) rat.
The Bio Breeding (BB) rat is a useful animal model of type 1 autoimmune diabetes. The aim of this study was to observe and follow the cytokine and antigenic expressions within the islets of Langerhans in young non-diabetic, in pre-diabetic hyperglycemic, and in overtly diabetic animals. BB rats were therefore checked at day 21 up to day 90 of life for blood glucose, insulin levels, degree of islet infiltration, expression of proinflammatory and protective cytokines and antibodies including CD4, CD8, CD25, LFA-1, and ICAM-1. Animals were treated with insulin as they became diabetic. We found that islets of non-diabetic BB rats became positive to both IL-1beta and IL-4 very early on, confirming a local but intense production of both cytokines within the islets during the initial non-diabetic period. In addition, we observed that the production of these interleukins together with the expression levels of CD4 and CD25 are events predictive for type 1 diabetes onset in non-diabetic BB rats, as for non-obese diabetic (NOD) mice. In particular, the production of IL-1beta and IL-4 during the non-diabetic period together with the lack of enhancement of CD4 and CD25, indicating selective recruitment of activated T cells, may explain the failure of anti-diabetic treatments in this animal model of type 1 diabetes.
Papaccio
Gianpaolo
G
Department of Experimental Medicine, Section of Histology and Embryology, Second University of Naples, 5 via L. Armanni, 80138 Naples, Italy. gianpaolo.papaccio@unina2.it
Graziano
Antonio
A
d'Aquino
Riccardo
R
De Francesco
Francesco
F
Puca
Andrew
A
Pedullà
Marcella
M
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D051381:Rats; D011913:Rats, Inbred BB
D015703:Antigens, CD; D001786:Blood Glucose; D007328:Insulin; D053583:Interleukin-1beta; D015847:Interleukin-4