Inflammation is mediated by a variety of soluble factors, including a group of secreted polypeptides known as cytokines. Some cytokines act to make disease worse (proinflammatory cytokines), whereas others serve to reduce inflammation and promote healing (anti-inflammatory cytokines). Some chemokines are considered pro-inflammatory and can be induced during an immune response to recruit cells of the immune system to a site of infection, while others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development. Inflammatory chemokines function mainly as chemoattractants for leukocytes, recruiting monocytes, neutrophils and other effector cells from the blood to sites of infection or tissue damage. Certain inflammatory chemokines activate cells to initiate an immune response or promote wound healing.
Inflammatory chemokines are formed under pathological conditions (on pro-inflammatory stimuli, such as IL-1, TNF-alpha, LPS, or viruses) and actively participates in the inflammatory response attracts immune cells to the site of inflammation. Examples are: CXCL-8, CCL2, CCL3, CCL4, CCL5, CCL11, CXCL10.
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Homeostatic chemokines constitutively produced in certain tissues and are responsible for basal leukocyte migration. These include: CCL14, CCL19, CCL20, CCL21, CCL25, CCL27, CXCL12 and CXCL13. This classification is not strict, for example CCL20 can act also as pro-inflammatory chemokine.
Figure | Decoy receptors and tuning of innate and adaptive immunity in peripheral tissues. Chemokine decoy receptors expressed on blood and lymphatic vessels, and in infiltrating leukocytes, cooperate in a coordinated action for the control of local inflammatory reactions and adaptive immunity. Duffy antigen receptor for chemokines (DARC) is expressed on blood vessels and erythrocytes and might have several mechanisms of action, including acting as a depot for chemokines on erythrocytes, as a decoy receptor on endothelial cells and as a transporter of chemokines through cell barriers (trancytosis). D6 is expressed on the lymphatic endothelium, as well as by leukocytes at lower levels, and scavenges pro-inflammatory chemokines, preventing excessive chemokine transfer to lymph nodes. CCX-CKR has been shown to be expressed by dendritic cells (DCs) and selected lymphocyte subpopulations in vitro and might have a role in the formation of tertiary lymphoid structures by controlling levels of agonists for CC-chemokine receptor 7 and CXC-chemokine receptor 5. NK, natural killer.
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2. Alberto M, et al. (2006). Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nature Reviews Immunology. 6, 907-918.
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