title: Early prophylaxis with recombinant human interleukin-11 prevents spontaneous diabetes in NOD mice.
abstract: 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.
authors.affiliation: Institute of Microbiology, University of Milan, Italy. ferdinic@ctonline.it
authors.forename: F
authors.initials: F
authors.lastname: Nicoletti
authors.forename: P
authors.initials: P
authors.lastname: Zaccone
authors.forename: I
authors.initials: I
authors.lastname: Conget
authors.forename: R
authors.initials: R
authors.lastname: Gomis
authors.forename: C
authors.initials: C
authors.lastname: Möller
authors.forename: P L
authors.initials: PL
authors.lastname: Meroni
authors.forename: K
authors.initials: K
authors.lastname: Bendtzen
authors.forename: W
authors.initials: W
authors.lastname: Trepicchio
authors.forename: S
authors.initials: S
authors.lastname: Sandler
mesh_terms: D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003520:Cyclophosphamide; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D004768:Enterotoxins / Q000633:toxicity; D005260:Female; D006801:Humans; D017370:Interleukin-11 / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000097:blood; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001786:Blood Glucose; D004768:Enterotoxins; D017370:Interleukin-11; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C031818:enterotoxin B, staphylococcal; D003520:Cyclophosphamide