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considered when studying the relationships that may exist between the cytokines and nutritional status.

The Nature of the Cytokines
Biochemistry

Almost all cytokines are glycoproteins secreted from a variety of cell types (Casciari et al., 1996). Recombinant cytokines have been expressed in bacterial systems where glycosylation does not occur and seem to have equivalent biological activity, at least vitro. However, the state of glycosylation may have some effect on the stability of cytokines in the circulation, and perhaps on biological half-life. Most cytokines work as monomers, although some exist as homodimers (for example, interleukin [IL]-10), heterodimers (for example, IL-12), and trimers (for example, tumor necrosis factor-alpha [TNF-α]).

Mode of Action

The cytokines act by binding specifically to receptors on the surface of target cells. Most cytokine receptors have been well characterized, and many have been isolated, sequenced, and cloned. Some receptors belong to the immunoglobulin superfamily, that is, they consist of glycoproteins with characteristic intra- and interchain disulfide bonds forming looped structures. Other cytokines use receptors in the 7-transmembrane family, which is known to work through the activation of intracellular G-proteins. Receptor structures vary from single chains to multimers of two or three chains. Also, some receptor peptide chains are shared among receptors for more than one cytokine. In some cases the receptors may be present (at low levels) on resting target cells; when these cells are activated during immune responses, the receptors increase in number. In other cases, receptors appear de novo following activation. This is an important characteristic of cytokine regulation.

Principles of Cytokine Action

Janis Kuby, in her textbook, Immunology (1994), notes three basic principles that must be taken into account when studying cytokines. First, the cytokine molecules tend to be very pleiotropic. That is, each one has numerous biological functions. At first, the cytokines were described in terms of their functional activities, for example "T-cell growth factor" (now, IL-2). However, when the cytokines were isolated and their amino acid sequences were determined, it was found that many molecules with diverse biological activities were, in fact, the same. So for instance, the molecule called interleukin-1 or IL-1 has at least 50 unique, separate names related to unique, separate biological



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