Critical Role of Proinflammatory Cytokine IL-6 in Allograft Rejection and Tolerance

被引：83

作者：

Zhao, X. ^{[1
,2
,3
]}

Boenisch, O. ^{[1
,2
]}

Yeung, M. ^{[1
,2
]}

Mfarrej, B. ^{[1
,2
]}

Yang, Sunmi ^{[1
,2
]}

Turka, L. A. ^{[4
,5
]}

Sayegh, M. H. ^{[1
,2
]}

Iacomini, J. ^{[1
,2
]}

Yuan, X. ^{[1
,2
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplantat Res Ctr, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA

[3] Nanjing Drum Tower Hosp, Dept Urol, Nanjing, Jiangsu, Peoples R China

[4] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Transplant Inst, Boston, MA 02215 USA

[5] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Transplant Immunol, Boston, MA 02215 USA

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2012年 / 12卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Allograft tolerance; CD4; costimulation blockade; CTLA4Ig; IFN-; IL-6; IL-17; rejection; transplantation; T-CELL SUBSETS; TRANSPLANTATION; SIGNAL; FAMILY;

D O I：

10.1111/j.1600-6143.2011.03770.x

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

The proinflammatory cytokine IL-6 plays an important role in controlling T-cell differentiation, especially the development of Th17 and regulatory T cells. To determine the function of IL-6 in regulating allograft rejection and tolerance, BALB/c cardiac grafts were transplanted into wild-type or IL-6-deficient C57BL/6 mice. We observed that production of IL-6 and IFN-? was upregulated during allograft rejection in untreated wild-type mice. In IL-6-deficient mice, IFN-? production was greater than that observed in wild-type controls, suggesting that IL-6 production affects Th1/Th2 balance during allograft rejection. CD28-B7 blockade by CTLA4-Ig inhibited IFN-? production in C57BL/6 recipients, but had no effect on the production of IL-6. Although wild-type C57BL/6 recipients treated with CTLA4-Ig rejected fully MHC-mismatched BALB/c heart transplants, treatment of IL-6-deficient mice with CTLA4-Ig resulted in graft acceptance. Allograft acceptance appeared to result from the combined effect of costimulatory molecule blockade and IL-6-deficiency, which limited the differentiation of effector cells and promoted the migration of regulatory T cells into the grafts. These data suggest that the blockade of IL-6, or its signaling pathway, when combined with strategies that inhibit Th1 responses, has a synergistic effect on the promotion of allograft acceptance. Thus, targeting the effects of IL-6 production may represent an important part of costimulation blockade-based strategies to promote allograft acceptance and tolerance.

引用

页码：90 / 101

页数：12

共 27 条

[1]

[Anonymous], P NATL ACAD SCI US

[2] Interleukin-6 (IL-6) prevents activation-induced cell death: IL-2-independent inhibition of Fas/fasL expression and cell death [J].