Cytokine synthesis inhibitor factor

IL-10, previously known as cytokine synthesis inhibitor factor (CSIF), was originally identified as a product of murine Th2 clones that suppressed the production of cytokines by ThI clones responding to stimulation of antigen (Fiorentino etal., 1989). In humans, ThO, ThI and TH2-like T cell clones, activated monocytes... 

Interleukin-10 (IL-10)—originally called cytokine synthesis inhibitory factor— appears to act chiefly as an inhibitor of cytokine synthesis (M45). However, it has also been reported that lL-10 is a growth factor for immature and mature T cells (M2) and stimulates cytotoxic T-cell differentiation (C21). 

Kitamura M, Suto T, Yokoo T, Shimizu F, Fine LG Transforming growth factor-(Jj is the predominant paracrine inhibitor of macrophage cytokine synthesis produced by glomerular mesangial cells. J Immunol 1996 156 2964-2971. 

After damage or infection, monocytes and KCs in the area detect the damaged cells or infectious agent and respond with release of primary mediators such as TNFa, IL-1 and some IL-6. These cytokines activate the surrounding cells, that respond with a secondary, amplified release of cytokines. This second wave includes large amounts of IL-6, which induce the synthesis of acute phase proteins in hepatocytes and chemoattractants such as IL-8 and MCP-1. These events will then lead to the typical inflammatory reactions. Both IL-1 and TNFa activate the central regulatory protein of many reactions involved in immunity and inflammation, nuclear factor kappa B (NFkB). These cytokines cause dissociation of NFkB from its inhibitor IkB, which makes translocation of NFkB to the nucleus possible. In the nucleus active NFkB induces the transcription of the second wave cytokines (see also Chapter 7 for the molecular mechanisms of cytokine-mediated cell activation). 

Anti-inflammatory effects Glucocorticoids have a dramatic effect on the distribution and function of leukocytes. These drugs increase neutrophils and decrease lymphocytes, eosinophils, basophils, and monocytes. The migration of leukocytes is also inhibited. The biochemical mechanisms underlying these cellular effects include the induced synthesis of an inhibitor of phospholipase A2 (see Chapter 18), decreased mRNA for COX-2, decreases in IL2 and IL3, ind decreases in platelet activating factor (PAF), an inflammatory cytokine. 

Fig. 15.3 Pathogenesis of acute vascular rejection. Activation of endothelium by xenoreactive antibodies (Ab), complement (C), platelets, and perhaps by inflammatory cells (natural killer (NK) cells and macrophages (M0) leads to the expression of new pathophysiologic properties. These new properties, such as the synthesis of tissue factor (TF) and plasminogen activator inhibitor type 1 (PAI-1), promote coagulation the synthesis of -selectin and cytokines such as ILIa promote inflammation. These changes in turn cause thrombosis, ischemia, and endothelial injury, the hallmarks of acute vascular rejection. (Adapted from Nature 1998 392(Suppl.) 11-17, with permission.)...

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