ORCHIECTOMY INCREASES BONE-MARROW INTERLEUKIN-6 LEVELS IN MICE

Interleukin-6 (IL-6) appears to be an important factor in disease stat es associated with bone resorption. There is both in vitro and in vivo evidence supporting the fact that androgens down-regulate interleukin -6 production. These observations, in combination with the fact that o steoblasts and bone marrow stromal cells produce IL-6, led us to hypot hesize that orchiectomy-induced androgen loss will result in increased IL-6 expression in the bone microenvironment. To prove our hypothesis we assessed the effect of orchiectomy on IL-6 protein and mRNA expres sion in bone marrow and spleen. We found that orchiectomy was associat ed with increased serum IL-6 levels at 3 and 28 days postsurgery. Phor bol ester-stimulated IL-6 levels were also higher in supernatants from bone marrow and spleen cell cultures from orchiectomized mice compare d with unoperated or sham-operated mice. Additionally, we found that s teady state IL-6 mRNA levels were increased in bone marrow but not spl een cells. Finally, we found that orchiectomized mice had splenomegaly and increased bone marrow cellularity. Histopathology of the spleen r evealed lymphoid hyperplasia accompanied by a marked mononuclear cell infiltration of the red pulp. We conclude that orchiectomy induces IL- 6 expression in the bone marrow. These findings suggest that endocrine and cytokine interactions contribute to bone pathophysiology.