Table 1 Pleiotropic effects of IL-6
From: IL-6 and the dysregulation of immune, bone, muscle, and metabolic homeostasis during spaceflight
TARGET | EFFECT |
|---|---|
B cells | Controls the proliferation, maturation and survival of B cells and plasmablasts; initiates T-cell-dependent and -independent isotype switching and antibody production; promotes the differentiation of IL-10+ B regulatory (B1) cells [IL-1β], and IL-21 production in CD4+ T cells to drive STAT-3 dependent plasma cell development. |
T cells | Regulates trafficking of lymphocytes, monocytes and macrophages and initiates transition from granulocytic to mononuclear cell infiltration at sites of inflammation; upregulates expression of surface markers involved in antigen presentation and phagocytosis; promotes the differentiation of Th2 [IL-4], Th17 [TGF-β], Th22 [TNF-α], Treg [IL-27], and Tfh [IL-21] cells; initiates the secretion of IL-10 by IFN-γ+ Th1, IL-4+ Th2 and IL-17+ Th17 cells [IL-27]; facilitates T-cell survival; inhibits Th1 differentiation [IFN-γ] and TNF-α and IL-1β secretion; enhances IL-2, IL-4, IL-10, IL-1ra secretion and IL-2R expression; stimulates TCR independent CD8+ T-cell proliferation and effector functions [IL-7 or IL-15]. |
Monocytes, dendrocytes | Promotes monocyte and dendrocyte to macrophage differentiation and IL-10+ M2 macrophage (M2d) activation. |
Hematopoietic progenitors | Promotes proliferation of multipotential hematopoietic cells, including the maturation of megakaryocytes [IL-3]. |
Hepatocytes | Initiates acute phase protein synthesis. |
Bone | Promotes bone formation by enhancing OB differentiation from mesenchymal cell precursors, by inhibiting OB apoptosis, and by augmenting immune cell secretion of IL-4, IL-10 and IL-1ra; inhibits bone resorption by decreasing OC RANKL expression, by upregulating OPG secretion in bone and B cells, and by inhibiting immune cell secretion of IL-1α/β and TNF-α; enhances OB activity in response to bone loading signals by releasing osteoclast-derived coupling factors/transmitters. |
Muscle | Increases glucose uptake and mitochondrial fatty acid oxidation by activating AMPK, P13K. Promotes myocyte differentiation, proliferation, and response to injury. Promotes post-exercise extracellular matrix reorganization and stem cell niche accumulation. |
Metabolic homeostasis | Restores CNS sensitivity to insulin, leptin; prevents obesity, glucose intolerance; increases pancreatic beta cell viability and insulin secretion; induces lipolysis, fat oxidation in hepatocytes, adipocytes. |
