We evaluated the effects of recombinant human (rh) interleukin (IL)-11 on the development of spontaneous and cyclophosphamide-induced diabetes in female NOD mice. Prolonged treatment with rhIL-11 10 microg i.p. five consecutive times a week between the 4th and 22nd weeks of age significantly suppressed both development and cumulative incidence of type 1 diabetes. Disease protection was transient because most of the animals developed type 1 diabetes within 3 months of treatment withdrawal. In contrast, rhIL-11 failed to prevent type 1 diabetes when administered for the first time to euglycemic 18-week-old NOD mice. Most likely, this discrepancy was not due to age-dependent differences in the immunological responses of NOD mice to rhIL-11 because staphylococcus aureus enterotoxin B-induced tumor necrosis factor (TNF) and IL-12 production were equally suppressed by rhIL-11 in 12- and 25-week-old NOD mice. Relative to controls, NOD mice pretreated with rhIL-11 also showed significantly diminished blood levels of TNF, interferon-gamma, and IL-12 induced by anti-CD3 antibody and/or lipopolysaccharide. The results demonstrate that rhIL-11 has powerful anti-inflammatory effects that are capable of down-regulating early immunodiabetogenic pathways in NOD mice.
|Titolo:||Early prophylaxis with recombinant human interleukin-11 prevents spontaneous diabetes in NOD mice|
|Parole Chiave:||Interleukin-11 ; Animals ; Tumor Necrosis Factor-alpha ; Interleukin-12 ; Recombinant Proteins ; Humans ; Mice, Inbred NOD ; Aging ; Mice ; Cyclophosphamide ; Blood Glucose ; Diabetes Mellitus, Type 1 ; Enterotoxins ; Time Factors ; Female ; Male|
|Settore Scientifico Disciplinare:||Settore MED/16 - Reumatologia|
|Data di pubblicazione:||dic-1999|
|Digital Object Identifier (DOI):||10.2337/diabetes.48.12.2333|
|Appare nelle tipologie:||01 - Articolo su periodico|