Antigen induced arthritis (AIA) can be transferred by bone marrow transplantation: evidence that interleukin 6 is essential for induction of AIA.

Abstract

To investigate the role of bone marrow cells (BMC) in the induction of antigen induced arthritis (AIA), the expression of 3 major proinflammatory cytokines, interleukin 1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6, was examined in the bone marrow (BM) of mice with AIA. We also examined whether AIA could be transferred by bone marrow transplantation (BMT). Expression of IL-1beta, TNF-alpha, and IL-6 in BMC was assessed by immunohistochemistry throughout the course of AIA. BMT experiments were performed using 2 different mouse genotypes, wild type (IL-6+/+) and IL-6 deficient (IL-6-/-) mice, as a donor. The gradation of AIA was evaluated histologically. IL-6 was highly expressed in the BM at induction as well as during progression of AIA, while TNF-alpha showed a marginal expression, and no significant expression of IL-1beta was detected throughout the course of AIA. In BMT experiments, all irradiated IL-6+/+ mice developed typical AIA by transplantation of BMC from immunized IL-6+/+ mice, whereas almost no irradiated IL- 6+/+ mice transplanted with BMC from the immunized IL-6-/- mice developed definite arthritis. These results suggest that BMC play a critical role and IL-6 is a key cytokine for the induction and progression of AIA. There may be clinical benefits in the blockade of IL-6 and BMT in the treatment of rheumatoid arthritis.