Immune system function is coordinated with and interacts with the nervous system. The transmission of signals from skin afferent nerve endings is in part modulated by immune mediators. The relevance with respect to itch is most clearly seen with release of histamine by mast cells. The result is the abrupt onset of uncomfortable itching. One treatment utilized in CKD-aP is ultraviolet light therapy, which reduces mast cell number and provides partial relief from itching.[21,22] Accordingly, it is surprising that antihistaminic drugs are not particularly effective for treating CKD-aP. Other aspects of immune system function are dysregulated in CKD, with a state of chronic inflammation being, especially notable among patients on dialysis. One result is an increase in a number of mediators that are associated with CKD-aP, including IL-2, IL-6, and IFN-γ and markers of inflammation such as C-reactive protein and IL-6.[16,23] One mediator of note is IL-31. This agent is associated with itch and connects the immune and nervous systems. Recent studies of the investigational drug, nemolisumab, are testing IL-31 blockade as a means of treating CKD-aP. Taken together it is clear that immune dysregulation plays a part in CKD-aP, but the precise role remains to be fully elucidated.
Curr Opin Nephrol Hypertens. 2022;31(5):435-441. © 2022 Lippincott Williams & Wilkins