Cytokine family

The cytokine family continues to grow, and often a decision to include a regulatory protein in this category is not a straightforward one. The following generalizations may be made with regard to most cytokines ... 

Although all cytokines are polypeptide regulatory factors, not all polypeptide regulatory factors are classified as cytokines. Classical polypeptide hormones, such as insulin, FSH and GH are not considered members of the cytokine family. The distinguishing features between these two groups is ill defined, and in many ways artificial. Originally, one obvious distinguishing feature was that hormones... 

Some cytokines have already gained approval for medical use. Many more are currently undergoing clinical or preclinical trials. Over the next few chapters the biology and potential medical applications of these cytokines will be discussed in detail. The remainder of this chapter concerns itself with the prototypic cytokine family, namely the interferons. 

Interleukin-6 (IL-6) is a member of the gpl30 cytokine family and is con-stitutively produced by several cells of bone microenvironment, particularly by osteoblasts and their precursors (Heymann et al. 2000). The main function in bone is on OCS and bone resorption, and its effects are connected to those of IL-1, TNF-a, and PTHrP. IL-6 induces osteoclastlike formation by inducing IL-1 synthesis, and the addition of anti-IL-1 inhibits osteoclast formation by IL-6 (Kurihara et al. 1990). Moreover, IL-6 mediates the effects of TNF-a and enhances PTHrP-induced hypercalcemia and bone resorption by increasing the osteoclast progenitor pool and differentiation into mature osteoclasts (Devlin et al. 1998). 

Heymann D, Rousselle AV (2000) gpl30 Cytokine family and bone cells. Cytokine 12 1455-1468... 

Cytokines are a heterogenous group of polypeptide mediators that have been associated with activation of numerous functions, including the immune system and inflammatory responses. The cytokine families include, but are not limited to, interleukins, chemokines, tumor necrosis factors, interferons (INF-a, -0, and -y), colony-stimulating factors, growth factors, neuropoietins, and neurotrophins (see Table 13.4). 

PF4. CXCL4. Belongs to inflammatory cytokines family, mediates the relationship between monocytes and endothelial cells, induces neutrophil adhesion and secondary granule exocytosis, and influences macrophages adhesion to endothelial cell by triggering monocyte arrest in atherosclerotic arteries... 

One of the interesting questions is why this approach has not been reported to have been used to successfully identify new members of other families of cytokines, such as the four helix bundle family which includes IL-2, IL-4, IL-5, etc. One problem for these families is that the defining features are not so apparent (for example the positions of the disulfide bonds are not always conserved). Also, the majority of the members of these cytokine families are only finally confirmed once their three-dimensional structures have been solved. It may be that when more sophisticated versions of such techniques as Profile searching can be used will this then open up new cytokines for more classical families. Such Profiles would have to include amino acid similarities, as well as secondary structure propensity. Even so, the current rate of success is not expected to be as high as for the chemokine area (see, for example, ref. 15). 

Oppenheim, J. J., Zachariae, C. O., Mukaida, N and Matsushima, K. (1991) Properties of the novel proinflammatory supergene intercrine cytokine family. Annu. Rev. Immunol. 9, 617-648. 

Monoclonal antibodies (MAbs) produced through the technique of somatic cell fusion are fundamental tools in the exploration of chemokine biology. This chapter details the procedures that were used to generate a panel of MAbs directed against the human chemokine RANTES (1,2). The general approach described here should be broadly applicable to the generation of MAbs directed against other members of this cytokine family. 

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