CYTOKINES IN IMMUNE SYSTEM
TNF-alpha: Amplifies T effector cell response How does TNF-alpha act, and can we target its down stream target CJSAN 2015 TNF-alpha signaling cascade includes JAK pathways. Inhibition of JAK pathway (JAK1, and JAK3 by Tofacitinib led to similar efficacy as Adalimumab in RA. Ofnote, significant side effects (sepsis, neutropenia, elevated Liver enzymes, elevated Cr) were seen as it probably also lacks specificity. From Kelly and Firestein's IL-6 Source: Monocyte, Fibroblast, T cell, B Cell Source: primarily produced by monocytes, fibroblasts and endothelial cells, and by T cells, B cells, keratinocytes and mesangial cells.2 http://dx.doi.org/10.1136/annrheumdis-2016-209668 Function of IL 6: IL 6 level is increased in RA and PsA but is also noted to be increased in SLE. What is the source of IL6 in Lupus? pDC (monocyte) ? or Fibroblast ? or T cell ? or B Cell What is mononulear phagocytes system? It includes Monocyte, Dendritic cells and Marophage. It also include Osteocalsts. In vitro, bone marrow precursors and blood monocytes can be stimulated by growth factors23 to generate macrophages (M-CSF or granulocyte-macrophage colony-stimulating factor [GM-CSF]), DCs (GM-CSF, with or without IL-4), or osteoclasts (M-CSF and receptor activator of nuclear factor-κB [NF-κB] [RANK] ligand) DC are professional APC. 3 major subtypes of DC 1) pDC 2) conventional DC 3) monocyte derived DC pDC is specialized to produce high level of INF What are Monocytes? BM contributes to circulating monocytes. In response to inflammatory stimulation, circulating monocytes gives rise of macrophage, dendritic cells and osteoclast. |