Poly I:C induces development of diabetes mellitus in BB rat.
Polyinosinic polycytidilic acid (poly I:C), an inducer of alpha-interferon, accelerates the development of diabetes in diabetes-prone (DP) BioBreeding (BB) rats. This study investigates the effect of administering poly I:C to a diabetes-resistant (DR) strain of BB rats. We compared the incidence of diabetes, the degree of insulitis, the number of NK cells, helper-inducer cells, cytotoxic-suppressor cells, Ia+ T cells, RT6.1+ T cells, and NK cell bioactivity in DR rats treated with saline and with a 5 micrograms/g body wt (poly-5) dose and a 10 micrograms/g body wt (poly-10) dose of poly I:C. The incidence of diabetes was also compared with that of DP rats receiving poly-5. We found that both doses of poly I:C significantly induce the development of diabetes in the DR BB rat. However, treatment of DR rats with the higher dose induces a greater rate of development of diabetes and earlier onset of diabetes than the lower poly-5 dose. The rate of diabetes development and the mean age of onset were similar in poly-10-treated DR and poly-5-treated DP rats. A significant degree of insulitis occurred in all the poly I:C-treated DR rats, even those not developing diabetes. Peripheral blood NK cell number was greater in poly I:C than in saline-treated rats, after 2 wk of treatment and when killed. The percentage of OX19+ peripheral blood mononuclear cells expressing RT6.1 allotype or Ia antigen were similar in poly I:C- and saline-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Sobel
D O
DO
Department of Pediatrics, Georgetown University School of Medicine, Washington, DC.
Newsome
J
J
Ewel
C H
CH
Bellanti
J A
JA
Abbassi
V
V
Creswell
K
K
Blair
O
O
D036002:ADP Ribose Transferases; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D011070:Poly I-C / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D011913:Rats, Inbred BB / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000473:pathology
D000945:Antigens, Differentiation, T-Lymphocyte; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D036002:ADP Ribose Transferases; C090163:Art2b protein, rat; D011070:Poly I-C