Chemokines (a shortening of chemoattractant cyto
kines) represent a superfamily of about 30 chemotactic cytokines
acting as vital initiators and promulgators of inflammatory
reactions. They range from 8 to 11 kD in molecular weight, are
active over a 1 to 100 ng/ml concentration range, and are produced
by a wide variety of cell types. The production of chemokines is
induced by exogenous irritants and endogenous mediators such as
IL-1, TNF-
, PDGF, and IFN-
. The chemokines bind to specific cell
surface receptors and can be considered second-order
cytokines that appear to be less pleiotropic than
first-order proinflammatory cytokines because they are not potent
inducers of other cytokines and exhibit more specialized functions
in inflammation and repair.
The chemokine molecules share structural similarities, including four conserved cysteine residues which form disulphide bonds in the tertiary structure of the proteins. Traditionally, the chemokine superfamily has been divided into two subgroups: C-X-C (where X is any amino acid) and C-C, according to whether an intervening residue spaces the first two cysteines. This structural distinction has been shown to delineate a general, though not absolute, distinction in the biological properties of these molecules: most C-X-C chemokines are chemoattrastants for neutrophils (and to some extent lymphocytes) but not monocytes, whereas C-C chemokines appear to attract monocytes, basophils, eosinophils, and lymphocytes (including NK cells) but not neutrophils. Recently, the third ''C'' branch of these molecules has been discovered. Lymphotactin, the representative of these C chemokines, is clearly chemoattractant for lymphocytes and NK cells, but it does not attract either monocytes or neutrophils. The list of main chemokines is in the Table 1.10 and 1.11.
Table 1.11: The main chemotactic factors for leukocytes
Not all of the known properties of the chemokines involve leukocyte migration. For example chemokines have been reported to have roles in haematopoietic precursor cell cycling regulation and differentiation. On the other hand, their involvement in such processes as leukocyte trafficking and inflammatory processes further suggest that the chemokines are important in a number of disease states. It is now clear that certain C-C chemokines, namely RANTES, MCP-1, MCP-3 and MIP-1 exhibit potent promigratory and activating potentials for eosinophils, basophils and T cells, the cells most often associated with respiratory pathologies and allergic disorders, including asthma and nasal polyposis. These observations are now being coupled with an emerging body of evidence showing that these mediators can be localized to affected tissues during these pathologies.
IL-8 and MCP-1 are more widely produced than other chemokines and there is a suggestion that they represent the first line of defence.
Interleukin-8 is a polypeptide consisting of 72 amino acids in its mature form. The biological profile of activity of IL-8 is very similar to that of the classical chemotactic peptides C5a and FMLP (N-formyl-methionyl-leucyl-phenylalanine). It is able to induce the full pattern of responses observed in chemotactically stimulated neutrophils, i.e. activation of the motile apparatus and directional migration, expression of surface adhesion molecules, release of lysosomal enzymes, and production of reactive oxygen intermediates. IL-8 is not species-specific and is a potent angiogenic factor.
Recently, elevated urinary IL-8 levels were observed in patients with several types of glomerulonephritis including IgA nephropathy, acute glomerulonephritis, purpura nephritis, membranous proliferative glomerulonephritis, and lupus nephritis, but not in patients with focal glomerulosclerosis and membranous nephropathy. The former groups are characterized pathologically by the infiltration of neutrophils and/or mononuclear cells and proliferation of mesangial cells, whereas the latter lacks such findings. Immunohistochemical analyses demonstrated the detection of IL-8 protein in inflammatory cells infiltrated into glomeruli in IgA nephropathy, suggesting that IL-8, produced in glomeruli, promotes the infiltration of neutrophils into glomeruli, thereby inducing renal injury.
Monocyte chemoattractant protein -- 1 (MCP-1) is
a chemoattractant for human monocytes with the optimal agonist
concentration of 
mol/L and may play a role in the
accumulation of monocytes over a period of 24-48 hours after
interaction of antigen and sensitized lymphocytes. MCP-1 is nearly
as effective as C5a, and much more potent than IL-8, in the
degranulation of basophils, resulting in histamine release. This
may play an important role in the pathogenesis of the late phase
of allergic disorders such as atopic food allergies, asthma, and
chronic urticaria. Histamine release also occurs after stimulation
with two other C-C chemokines, RANTES and MIP-1
.