The effect of intravenous immunoglobulins on intimal thickening in a mouse model of arterial injury.
Inflammatory mechanisms appear to influence the progression of intimal thickening in experimental models of arterial injury. Intravenous immunoglobulin (IVIG) is a polyspecific preparation of human immunoglobulin (Ig)G employed for treatment of autoimmune disorders. In this study, we sought to investigate whether treatment with IVIG could influence intimal thickening in a model of murine arterial injury. Intimal thickening was induced by placement of a periadventitial cuff over the right femoral artery of male C57BL/6 mice. In the first experiment, IVIG or human serum albumin (HSA) (10 mg/mouse) were administered intraperitoneally for five consecutive days starting 1 day prior to cuff placement. In the second experiment, IVIG or HSA treatment were delivered similarly, but initiated 3 days following induction of arterial injury. Neointimal area and intimal/medial ratio were significantly reduced in mice treated with IVIG prior to cuff placement as compared with HSA treatment. No differences were noted with regard to neointimal area or intimal/medial ratio, between IVIG- and HSA-treated mice when the treatment was commenced 3 days following induction of injury. IVIG treatment reduced the proliferative capacity of splenocytes to the non-specific mitogen Con-A. Treatment with IVIG was associated with a significantly enhanced secretion of interleukin (IL)-10) by the respective splenocytes in comparison with HSA-treated mice. No effect of IVIG was evident on the secretion of IL-4 or IFN-gamma. Thus, IVIG has proven beneficial in ameliorating intimal thickening in a mouse model of arterial injury. The effect could be mediated by upregulation of T-cell secretion of the anti-inflammatory cytokine IL-10.
Keren
G
G
Department of Cardiology and the Cardiovascular Research Laboratory, Ichilov Hospital, Elias Sourasky Tel-Aviv Medical Center, 6 Weizman Street, Tel-Aviv, Israel. kereng@tasmc.health.gov.il
Keren
P
P
Barshack
I
I
Pri-Chen
S
S
George
J
J
D000818:Animals; D005263:Femoral Artery / Q000293:injuries* / Q000473:pathology*; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012709:Serum Albumin / Q000494:pharmacology; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
D016756:Immunoglobulins, Intravenous; D012709:Serum Albumin; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma