Interleukin-6 chaperones in blood

There is increasing evidence that many, perhaps all, cytokines have a soluble form of their receptor in the systemic circulation at all times. There is also evidence that endogenous antibodies to some cytokines, including IL-6, are also found in blood. Initially these findings were evaluated in vitro, and associated with inhibiting the respective effects of those cytokines. However, it is now becoming clear that the in vivo effects are paradoxically the reverse of what is seen in vitro. As we have explained here for IL-6 it is evident that many or all of these molecules that bind and/or associate with IL-6 maintain this molecule in the systemic circulation and constitute a reservoir of masked, but potentially active IL-6. The mode of regulation of the biological activity of these IL-6-associated complexes remains unknown, but needs to be uncovered in order to pharmacologically exploit many of the potentially beneficial effects or to prevent any potential pathological effects.