Interleukin-6 deficiency increases inflammatory bone destruction

Periapical bone destruction occurs as a consequence of pulpal infection. In previous studies, we showed that interleukin-1 (IL-1) is the primary stimu lator of bone destruction in this model. IL-6 is a pleiotropic cytokine tha t is induced in these infections and has both pro- and anti-inflammatory ac tivities. In the present study, we determined the role of IL-6 in regulatin g IL-1 expression and bone resorption, The first molars of IL-6 knockouts ( IL-6(-/-)) and wild-type mice were subjected to surgical pulp exposure and infection with a mixture of four common pulpal pathogens, including Prevote lla intermedia, Fusobacterium nucleatum, Peptostreptococcus micros, and Str eptococcus intermedius. Mice were killed after 21 days, and bone destructio n and cytokine expression were determined, Surprisingly, bone destruction w as significantly increased in IL-6(-/-) mire versus that in wild-type mice (by 30%; P < 0.001). In a second experiment, the effects of chronic (IL-6-/ -) IL-6 deficiency and short-term IL-6 deficiency induced by in vivo antibo dy neutralization were determined, Both IL-6(-/-) (30%; P < 0.001) and anti -IL-6 antibody-treated mice (40%; P < 0.05) exhibited increased periapical bone resorption, compared to wild-type controls, The increased bone resorpt ion in IL-6-deficient animals correlated with increases in osteoclast numbe rs, as well as with elevated expression of bone-resorptive cytokines IL-1<a lpha> and IL-1 beta, in periapical lesions and with decreased expression of the anti-inflammatory cytokine IL-10, These data demonstrate that endogeno us IL-6 expression has significant anti-inflammatory effects in modulating infection-stimulated bone destruction in vivo.