We explored the mechanism for the increase of
blood IL-6 level after anti-IL-6 receptor (IL-6R)
antibody injection. First, we examined whether anti-IL-6R
antibody stimulates IL-6 production. Single injection of
tocilizumab (anti-IL-6R
antibody) in monkeys with collagen-induced
arthritis (CIA) caused a marked increase in
blood IL-6 and IL-6R levels, but did not increase IL-6
mRNA and IL-6R
mRNA expression in
liver,
spleen,
lymph nodes,
synovium or
whole blood 1, 3 and 7 days later. This suggests that
tocilizumab did not induce IL-6 and IL-6R production. Second, we investigated whether anti-IL-6R
antibody releases IL-6 from IL-6 complexes in the
blood. When plasma from CIA monkeys was incubated with
tocilizumab, the IL-6 concentration was not affected. Finally, we studied whether anti-IL-6R
antibody affects the clearance of IL-6 from the
blood. When MR16-1 (anti-mouse IL-6R
antibody) was injected into IL-6-deficient
mice continuously infused with human IL-6,
blood human IL-6 levels significantly increased. These results suggest that the elevation of
blood IL-6 after the administration of anti-IL-6R
antibody is the result of inhibition of the clearance of IL-6 due to IL-6R blockade, and that it is not the result of induction of IL-6 production or release of IL-6 from complexes.
