The findings that bone marrow fibroblastoid stromal cells are important for
activin A production prompted our investigation of activin A expression in
fibroblast-like synoviocytes in joint capsule in this and previous studies
. In the proliferative reactive synovial membrane obtained from rheumatoid
arthritis patients, activin A is detected prominently in the fibroblastoid
synovial cells, as well as in the smooth muscle and the endothelial layer o
f the arteries in these vascularized proliferative tissues. The concentrati
on of activin A in the rheumatoid arthritis synovial fluid was 33.6 +/- 5.0
ng/ml, much higher than the activin A content of osteoarthritis fluid (10.
0 +/- 1.1 ng/ml). Furthermore, our previous studies also showed that inflam
matory cytokines, such as interleukin (IL)-1, transforming growth factor (T
GF)-beta, interferon (IFN)-gamma, IL-8, and IL-10 markedly enhance the expr
ession of activin A mRNA in synoviocytes. These findings are consistent wit
h our studies in regard to the regulatory control of activin A production i
n bone marrow stroma and monocytes. In addition, the relationship of activi
n A to IL-6-induced biological activities in various cell types was also in
vestigated. Although activin A has not been directly associated with inflam
matory processes, future studies are needed to investigate its production i
n response to the accumulated levels of inflammatory cytokines in the synov
ium of the patients, as well as the quantitative differences in activin A c
oncentrations in many patients with other inflammatory diseases. (C) 2001 E
lsevier Science Ireland Ltd. All rights reserved.