Apolipoprotein E (apoE) is a multifunctional glycosylated protein characterized by its wide tissue distribution. Despite its importance in lipid transport and atherosclerosis pathogenesis, apoE is associated with neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson disease, and autoimmune disorders such as multiple sclerosis and psoriasis. Among others, the role of apoE in modulating inflammation and oxidation is crucial in elucidating the risk factors of the above diseases since the function of apoE is closely linked with both proinflammatory and antiinflammatory cytokines. Moreover, apoE modulates inflammatory and immune responses in an isoform-dependent manner. Correspondingly, inflammatory cytokines can either upregulate or downregulate the production of apoE in various tissue types. However, studies on the interactions between apoE and cytokines occasionally yield conflicting results, highlighting the complex roles of apoE and cytokines in various disorders. The present paper summarizes the current knowledge about the cross-talk between apoE and cytokines, with emphasis on the effects of apoE on the Th1/Th2 balance. 1. Introduction Apolipoprotein E (apoE) was first discovered in 1970s and identified as a component of triglyceride-rich lipoprotein complexes. Since then, apoE has been widely studied in lipid metabolism, cardiovascular diseases [1], and neurodegenerative disorders such as Alzheimer’s disease (AD) [2] and Parkinson disease (PD). In addition to its well-established role in lipid transportation and atherosclerostic pathogenesis, apoE bears immunomodulatory properties and is associated with multiple sclerosis (MS) [3] and psoriasis [4]. ApoE can modulate the functions of macrophages, suppress the proliferation of T cells, maintain the integrity of blood-brain barrier (BBB) and blood-nerve barrier (BNB), inhibit the proliferation of smooth muscle (SM) cells, upregulate the production of nitric oxide (NO) of platelets, facilitate the presentation of lipid antigen by CD1 molecules to natural killer T (NKT) cells, and so forth, (Figure 1). Cytokines are crucial in human inflammatory and autoimmune disorders and apoE might affect these disorders through interacting with cytokines. Figure 1: Schematic illustration of the biological properties of apoE. ApoE acts on adipocytes to maintain the triglyceride homeostasis; acts on hepatocytes to promote very low density lipoprotein (VLDL) production and lipoprotein clearance; modulates the functions of macrophages (MΦ); suppresses the proliferation of T cells; maintains the
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