Prevention of diabetes mellitus in non-obese diabetic mice by Linomide, a novel immunomodulating drug.
Oral administration of the synthetic immunomodulating drug quinoline-3-carboxamide (Linomide) in the drinking water to 5-week-old female non-obese diabetic (NOD) mice resulted in complete protection from insulitis and maintenance of normal glucose tolerance for over 40 weeks (impaired glucose tolerance: treated n = 2 of 18; control n = 17 of 18, p < 0.0001). Delayed administration of the drug at 16 weeks resulted in slowing of the progression to diabetes when assessed at 42 weeks (treated with diabetes n = 7 of 25; control with diabetes 25 of 43, p < 0.0234). No gross changes of immune system cell phenotype or function were observed in the Linomide-treated group. Adoptive transfer of spleen and lymph node cells from treated female NOD mice into sub-lethally irradiated male recipients failed to transfer diabetes, whereas a similar transfer of cells obtained from untreated age-matched controls resulted in diabetes in all secondary recipients (diabetes in control group n = 12 of 13; in Linomide group n = 0 of 11, p < 0.0001). Linomide pretreatment of the secondary recipients also inhibited the transfer of diabetes (diabetes in pretreated group n = 2 of 9, control group n = 12 of 13, p < 0.015), as did adoptive co-transfer of cell mixtures obtained from treated female NOD mice, free of diabetes, and from diabetic NOD female mice (diabetes in Linomide group n = 4 of 9; in control group 7 of 7, p < 0.0337).(ABSTRACT TRUNCATED AT 250 WORDS)
Gross
D J
DJ
Department of Endocrinology and Metabolism, Hadassah University Hospital, Jerusalem, Israel.
Sidi
H
H
Weiss
L
L
Kalland
T
T
Rosenmann
E
E
Slavin
S
S
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D003643:Death; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006912:Hydroxyquinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007515:Islets of Langerhans / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D013154:Spleen / Q000276:immunology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D006912:Hydroxyquinolines; C045282:roquinimex