Chapter 5.5 - Chemokines in the Inflamed Peripheral Nervous System

Abstract

Chemokines are involved in the composition of cellular infiltrates in immune-mediated demyelinating disorders of the peripheral nervous system (PNS). A consistent chemokine receptor expression pattern was immunohistochemically detected in inflammatory demyelinating neuropathies. The distribution of the two chemokines, IP-10 and RANTES, mirrored the distribution of equivalent receptors within the inflamed peripheral nervous system. Results from studies in experimental autoimmune neuritis, describing various maximum chemokine expression levels to be coincident with peak of clinical disease, suggest that these chemokines exert an amplifying rather than initiating role in generating PNS inflammation. Moreover, chemokines might also be involved in modulating the immune response during the course of the disease. It appears that RANTES, and potentially other chemokines, might exhibit beneficial effects by promoting axonal regeneration after axonal degeneration caused by severe demyelination. Therefore, it can be assumed that the PNS might have its own chemokine ligand–receptor network whose function could extend well beyond the regulation of leukocyte trafficking in immunoinflammatory disease. Further research is needed to understand the biological implications of this observation. Increased knowledge of the expression and specific function of individual chemokines and their receptors will hopefully help to design inhibitors that could be administered at critical checkpoints in the evolution of immune-mediated demyelination of the PNS.