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.