Cross talk between the immune system and the nervous system in response to injury: implications for regeneration

The central nervous system has long been regarded as an immunologically privileged site. Accumulating evidence suggests, however, that the privilege is not total, and that certain immune functions involving immune components and resident glial cells can operate in the central nervous system. The nervous and immune systems interact during normal development, but in the mature brain their interaction is restricted mainly to cases of pathogenic infections and traumatic lesions. The focus of this review is on bidirectional interactions between immune and neuroglial components in response to nerve injury. The macrophage is the most ubiquitous of the immune-derived cell types associated with injury. Its role, as in any other organ, is tissue remodeling and promotion of healing. Macrophage activities include removal of dead tissue and debris by phagocytosis, lipid recycling, and secretion of a wide spectrum of cytokines possessing trophic, mitogenic, and chemotactic properties. These activities affect the behavior of resident cells in the vicinity of the wound. We discuss the possible association of these cytokines with the ability of injured nerves to regenerate. Finally, we consider the apparently conflicting effects of posttraumatic inflammation on the recovery of function.