Respective roles of inflammation and axonal breakdown in the regulation ofperipheral nerve hemopexin: an analysis in rats and in C57BL/Wlds mice

We have previously demonstrated that one of the peripheral nerve responses to injury is the overexpression of hemopexin (HPX). Here, we demonstrate th at Wallerian degeneration is required for this response, since HPX does not increase in C57BL/Wlds mice, which display a severely impaired Wallerian d egeneration. We also show that HPX synthesis is dramatically increased in m acrophages during their activation or after IL-6 stimulation. However, IL-6 -driven HPX overexpression occurs in vivo and in vitro in the absence of su bstantial macrophage invasion. We conclude that, after nerve injury, HPX ov erexpression occurs first in Schwann cells as a result of axotomy and is su bsequently regulated by inflammation. Furthermore, our results and those al ready described suggest that IL-6, synthesized by the various cell types pr oducing HPX, control nerve HPX expression via paracrine and autocrine mecha nisms. (C) 2000 Elsevier Science B.V. All rights reserved.