Continuous interleukin-6 application in vivo via macroencapsulation of interleukin-6-expressing COS-7 cells induces massive gliosis

The inflammatory cytokine interleukin-6 (IL-6) was found in senile plaques of Alzheimer's patients and might be involved in the pathology of Parkinson 's disease and multiple sclerosis. Interestingly, an astocytosis is also fo und in these neurodegenerative disorders. To evaluate the direct effects of IL-6 in vivo on glial cells, we created a new in vivo model. IL-6 and mock -transfected (control group) COS-7 cells were encapsulated in a poly-acryl- nitril membrane for implantation into the rat striatum. Afterward, the host immune reaction to the membrane without encapsulated cells and the biologi cal action of IL-6-producing capsules was evaluated. Animals with an implan ted membrane without cells showed a moderate astrocytosis 5 days after the operation. Furthermore, microglia and T-cells could be detected and after 3 0 days the astrocytosis decreased to a small layer around the membrane. In comparison to the control group, which received a sham operation, our resul ts demonstrate that the response of glial cells is caused by the mechanical damage of the surgical procedure itself rather than due to the introduced membrane material. In contrast, we found a massive proliferation and activa tion of astrocytes and microglia after 10 days by IL-6-secreting capsules, indicating that IL-6 is involved in the induction of gliosis. Control anima ls that received encapsulated mock-transfected COS-7 cells showed only a we ak response. These data point to an involvement of IL-6 in the proliferatio n and activation of glial cells as seen in neurodegenerative disorders. (C) 2001 Wiley-Liss, Inc.