Intravenous immunoglobulins exposed to heme (heme IVIG) are more efficient than IVIG in attenuating autoimmune diabetes.
Intravenous immunoglobulins (IVIG) are known to have a therapeutic effect in some autoimmune diseases. We examined the effect of IVIG and heme-exposed IVIG on the development of immune mediated diabetes induced in C57BL/6 mice by multiple low doses of streptozotocin. IVIG were used in a dose of 200mg/kg daily for 15 days. Treatment with IVIG resulted in significant attenuation of diabetes induction as evaluated by glycemia, glycosuria and HbA1c level. Interestingly, heme-exposed IVIG had a still stronger antidiabetogenic effect. Serum levels of proinflammatory cytokines TNF-α, IFN-γ and IL17 were lower in IVIG treated animals when compared with controls, while IL10 level was higher. The number of CD4(+)Foxp3(+) cells was higher in pancreatic lymph nodes of heme-exposed IVIG treated mice. Our results show that IVIG may downregulate diabetes induction possibly by favouring induction of T regulatory cells and suggest enhanced effect upon heme-binding to IVIG.
Center for Molecular Medicine, Faculty of Medicine, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia.
Sladjana
S
Pavlovic
Nemanja
N
Zdravkovic
Jordan D
JD
Dimitrov
Aleksandar
A
Djukic
Nebojsa
N
Arsenijevic
Tchavdar L
TL
Vassilev
Miodrag L
ML
Lukic
D000818:Animals; D003520:Cyclophosphamide / Q000276:immunology; D016207:Cytokines / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D015536:Down-Regulation; D006442:Glycated Hemoglobin; D006029:Glycosuria / Q000276:immunology / Q000517:prevention & control; D006418:Heme / Q000276:immunology*; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology / Q000517:prevention & control; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D003520:Cyclophosphamide; D016207:Cytokines; D006442:Glycated Hemoglobin; D006418:Heme; D016756:Immunoglobulins, Intravenous