Monday 8 March 2004
Cytokines are soluble proteins produced by a wide variety of hemopoietic and non-hemopoietic cell types. They are critical to the functioning of both innate and adaptive immune responses.
Apart from their role in the development and functioning of the immune system, and their aberrant modes of secretion in a variety of immunological, inflammatory and infectious diseases, cytokines are also involved in several developmental processes during human embryogenesis.
Cytokines have been variously named as lymphokines, interleukins and chemokines, based on their presumed function, and their cell of secretion or target of action. In view of the fact that cytokines are characterised by considerable redundancy and pleotropism, such a distinction has, with few exceptions, become largely obsolete.
The term interleukin was initially used by researchers for those cytokines whose presumed targets are principally leukocytes. The term chemokine referred to a specific class of cytokines that mediated chemoattraction (chemotaxis) between cells. The latter term alone has been retained (see below); interleukins are now used largely for designation of newer cytokine molecules discovered every day, and have little significance attached to their presumed function. IL-8 (interleukin-8) is the only chemokine originally named an interleukin.
Cytokines have now been classified into four different types based on structural homology, which has been partly able to separate cytokines that do not demonstrate a considerable degree of redundancy.
Four α-helix bundle family, the three dimensional structures of whose members have four bundles of α-helices. This family inturn is divided into three sub-families, the IL-2 subfamily, the interferon (INF) subfamily and the IL-10 subfamily. The first of these three subfamilies is the largest, and contains several non-immunological cytokines including erythropoietin(EPO) and thrombopoietin (THPO).
IL-1 family, which primarily includes IL-1 and IL-18.
IL-17 family, which is yet to be completely characterised. However, it is known that they have a specific effect in promoting proliferation of T-cells that cause cytotoxic effects.
A more clinically and experimentally useful classification divides immunological cytokines into those that promote the proliferation and functioning of helper T-cells type 1 (example, IL-1, INF-γ etc.) and helper T-cells type 2 (IL-4, IL-10, IL-13, TGF-β etc.), respectively. It is remarkable that the cytokines that belong to one of these sub-sets tend to inhibit the effects of their counterparts - a tendency under intensive study for their possible role in the pathogenesis of autoimmune disorders.
The effects of cytokines are mediated by their binding to a specific cell-surface receptor and the subsequent initiation of various intracellular signalling cascades that produce a wide variety of effects on the functioning of the cell. This may include the upregulation and/or downregulation of several genes and their transcription factors, that result in production of other cytokines, or increase in the number of surface receptors for other molecules, or suppress their own effect by feedback inhibition.
Therefore, cytokines are characterised by considerable redundancy, in that many cytokines can share similar functions. In a similar manner, cytokines are also pleotropic, in that they are capable of acting on many different cell types. Of course, this would be an anticipated corollary if one considers the simple fact that a given cell type may express receptors for more than one cytokine, or that many different tissues can express receptors for the same cytokine.
Generalisation of functions is not possible with cytokines; nonetheless, their actions may be comfortably grouped as:
autocrine, if the cytokine acts on the cell that secretes it
paracrine, if the action is restricted to the immediate vicinity of a cytokine’s secretion
endocrine, if the cytokine diffuses to distant regions of the body (carried by blood or plasma) and mediates its effects on different tissues.