The dual roles of inflammatory cytokines and chemokines in the regulation of autoimmune diseases and their clinical implications

Journal of Leukocyte Biology

Nathan Karin¹  Idit Shachar, and³  *¹  Nathan Karin ²  Idit Shachar¹ 

[1] Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; and Department of Immunology, Rappaport Family Institute for Research in the Medical Sciences and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; and Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; and Department of Immunology, Rappaport Family Institute for Research in the Medical Sciences and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel Department of Immunology, Rappaport Family Institute for Research in the Medical Sciences and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; and Department of Immunology, Rappaport Family Institute for Research in the Medical Sciences and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel Department of Immunology, Rappaport Family Institute for Research in the Medical Sciences and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel Department of Immunology, Weizmann Institute of Science, Rehovot, Israel;Department of Immunology, Weizmann Institute of Science, Rehovot, Israel;

关键词: TGF-β;    IL-10;    IL-2;    IFN-γ;    CCL2;    CXCL12;   

DOI  :  10.1189/jlb.0612293

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Cytokines and chemokines are secreted, small cell-signaling protein molecules, whose receptors are expressed on immune cells. These factors play a critical role in immune cell differentiation, migration, and polarization into functional subtypes and in directing their biological functions. Much attention has been devoted to exploring the role of key inflammatory cytokines and promigratory chemokines in autoimmune, autoinflammatory, and allergic diseases, leading to development of therapeutic strategies that are based on their targeted neutralization. Recent studies, including those coming from our groups, show that several major proinflammatory cytokines and chemokines, including IFN-γ, IL-2, CCL2, and CXCL12, may also function as anti-inflammatory mediators and therefore, may have potential as anti-inflammatory drugs. Likewise, major anti-inflammatory mediators, such as TGF-β, may under certain conditions, in combination with other cytokines, exhibit proinflammatory function and direct the polarization of the highly inflammatory CD4+ Th17 cells. We show here that the biological function of pro- and anti-inflammatory cytokines is dependent on three key parameters: the local concentration of a given cytokine, the stage of disease in which it is administered, and its combination with other cytokines. The therapeutic implications of these findings are discussed, including two very recent studies summarizing clinical trials, in which low-dose administration of IL-2 was used to successfully suppress HCV and GVHD.

【 授权许可】

Unknown