INTERLEUKIN-6-TYPE CYTOKINES IN-VIVO - REGULATED BIOAVAILABILITY

Investigators have traditionally thought of the class of inflammation- acid injury-associated cytokines in large part as ''free'' entities i n 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 Ig G, and others. Sustained high levels of different particular IL-6 comp lexes are observed in the human circulation in cancer patients subject ed to particular active anticancer immunotherapy regimens. In the ''ch aperoned'' state, circulating IL-6 complexes display differential immu noreactivity in different ELISAs and possess differential biological a ctivity as assayed ex vivo, The discovery of ''chaperoned'' circulatin g IL-6 in humans points to a new level of modulation of cytokine funct ion, that of regulated bioavailability of IL-6 in vivo.