Factors Affecting the Measurement of Cytokines in Biological Fluids: Implications for Their Clinical Measurement

Cytokines, a term first used by Cohen, I are usually defined as soluble proteins, released by living cells of the host, which act to regulate host cell function. The first cytokines to be described had immunoregulatory effects, although it is now clear that this definition encompasses a wide variety of functions. A more precise definition is difficult because of the increasing number of such regulatory peptides which have been discovered. In general, cytokines are multifunctional molecules with diverse biological actions and target cells. Their main functions are usually local, modulating the behaviour of adjacent cells (paracrine) or the cell that secretes them (autocrine), but in some cases they have significant effects at distant sites. In normal conditions, cytokines are released in picomolar amounts, and only in certain pathological situations do they become detectable in significant amounts in peripheral blood. The term cytokines includes: the interleukins (interleukin-I to interleukin-14); tumour necrosis factor (TNF) a and (3; interferon (lFN) a, (3and -y; transforming growth factor (TGF) a and (3; chemokines (including monocyte chemoattractant protein and IL-8); haematopoietic growth factors; and others (see reviews/v' for discussion of individual cytokines). The most frequently measured cytokines are TNFa, interleukin-I (lL-I), interleukin-6 (I L-6)and more recently interleukin-8 (lL-8), all in the context of acute inflammation and infection. Measurements of IL-2 and soluble lL-2 receptor are proving of interest in the investigation of patients with immune-mediated disease and IL-5 in allergic disorders.