A noncytolytic IL-10/Fc fusion protein prevents diabetes, blocks autoimmunity, and promotes suppressor phenomena in NOD mice.
We have been successful in our efforts to develop a long lived noncytolytic murine IL-10/Fc fusion protein. In the nonobese diabetic mouse (NOD) model, administration of IL-10/Fc from 5 to 25 wk of age completely prevented the occurrence of diabetes. Moreover, these mice remained disease-free long after cessation of IL-10/Fc therapy. Immunohistochemistry studies show that IL-10/Fc treatment inhibits expression of TNF-alpha, proinflammatory cytokine, as well as Th1-type cytokines, IL-2 and IFN-gamma, but promotes expression of IL-4 and IL-10, Th2-type cytokines, by islet-infiltrating leukocytes. In an adoptive transfer model of diabetes in NOD mice, we found that: 1) IL-10/Fc treated hosts bear leukocytes that block expression of diabetes and 2) these leukocytes persisted even 8 wk after cessation of IL-10/Fc treatment. The potent antidiabetogenic effects provided by IL-10/Fc in the NOD model, together with its apparent lack of systemic toxicity, are notable.
Zheng
X X
XX
Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Steele
A W
AW
Hancock
W W
WW
Stevens
A C
AC
Nickerson
P W
PW
Roy-Chaudhury
P
P
Tian
Y
Y
Strom
T B
TB
D000208:Acute Disease; D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D005260:Female; D007116:Immunization, Passive; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry; D016753:Interleukin-10 / Q000737:chemistry / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD / Q000276:immunology*; D011993:Recombinant Fusion Proteins; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D016207:Cytokines; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D016753:Interleukin-10