Interleukin-6-type cytokines in vivo: regulated bioavailability.

Investigators have traditionally thought of the class of inflammation- and injury-associated cytokines in large part as "free" entities in the peripheral circulation. In the case of interleukin-6 (IL-6), the cytokine can be found in blood in complexes of molecular mass 400-500, 150-200, and 25-35 kDa in association with binding proteins that can include soluble IL-6 receptor (sIL-6R), anti-IL-6, and anti-sIL-6R IgG, and others. Sustained high levels of different particular IL-6 complexes are observed in the human circulation in cancer patients subjected to particular active anticancer immunotherapy regimens. In the "chaperoned" state, circulating IL-6 complexes display differential immunoreactivity in different ELISAs and possess differential biological activity as assayed ex vivo. The discovery of "chaperoned" circulating IL-6 in humans points to a new level of modulation of cytokine function, that of regulated bioavailability of IL-6 in vivo.