Regulation of Antibody-Dependent Cellular Cytotoxicity in Multiple Sclerosis by Central Nervous System Hormones

Abstract

Using oligodendrocytes from primary brain cultures as targets in an antibody-dependent cellular cytotoxicity (ADCC) assay, we have examined the effects of insulin and histamine on killer cells in multiple sclerosis (MS) and other neurological disease (OND) controls compared to normal healthy controls. The effects were shown to be specific for effectors by preincubation experiments. MS patients' ADCC to primary oligodendrocytes was depressed, but could be boosted to normal control levels by histamine binding to the H1 receptor. Significant elevation of MS ADCC by cimetidine alone suggested that endogenous histamine production and H2 receptor binding could be mediating a suppressive effect on MS ADCC to oligodendrocytes. In addition, MS ADCC could be boosted significantly by insulin. MS killer cells were more sensitive in vitro to the boosting effects of both histamine and insulin than either OND or normal controls, both in dose response and magnitude of the increased ADCC.