Contemplating IL-6, a double-edged sword cytokine: Which side to use for stroke pathology?

Interleukin (IL)-6 is a unique cytokine due to its dual signaling, with one pathway being pro-inflammatory (trans) and the other homeostatic (classical). Both of these pathways have been implicated in neuroinflammation following stroke, with initial inflammatory mechanisms being protective and later anti-inflammatory signaling promoting ischemic tissue recovery. IL-6 plays a major role in stroke pathology. However, given these distinctive IL-6 signaling consequences, IL-6 is a difficult cytokine to target for stroke therapies. Recent research suggests that the ratio between the pro-inflammatory binary IL6:sIL6R complex and the inactive ternary IL6:sIL6R:sgp130 complex may be a novel way to measure IL-6 signaling at different time points following ischemic injury. This ratio may approximate functional consequences on individualized stroke therapies, allowing clinicians to determine whether IL-6 agonists or antagonists should be used at specific time points.