Knowledge Bank

Stroke is a leading cause of death in the US and results in over $73.7 billion in health care costs every year. Strong social support has been shown to reduce mortality in cardiovascular disease and stroke, yet little is known about the physiological mechanism underlying these health benefits. Extensive tissue damage following stroke results in part from activated microglia, the immune cells of the brain. Oxytocin, a hormone released during social interaction, increases expression of Cluster of Differentiation 200 (CD200), a neuronal marker known to suppress microglial activation. We hypothesize that Interleukin-4 (IL-4), an anti-inflammatory cytokine produced by T-cells, is involved in the oxytocin-mediated mechanism through which social interaction conveys neuroprotection by upregulating expression of CD200 and complement receptor 1-related gene/protein-y (Crry). Using an animal model of social interaction, we show that oxytocin, IL-4, CD200, and Crry are increased in the brains of pair housed mice relative to isolated mice and that exogenous administration of IL-4 in vitro upregulates neuronal CD200, Crry, and oxytocin receptor gene expression. However, IL-4 does not alter oxytocin gene expression. An absence of IL-4 also eliminates the increase in CD200R found in paired mice compared to isolated mice. These findings further elucidate the physiological mechanism by which social interaction is beneficial to one’s health, and may lead to new methods to reduce the risk for and improving recovery from multiple diseases such as stroke and cardiac arrest.