Orchestrating neuroinflammation: A symphony of Interleukin-1 and cell type-specific Interleukin-1 receptor type 1 signaling in the brain.

Interleukin-1 (IL-1) was one of the first inflammatory cytokines to be discovered in the peripheral immune system. It is a master regulator of the inflammatory responses to infection and injury in the entire body. Infection and injury to the central nervous system (CNS) inevitably activate the IL-1 system similar to the periphery. While the existence of inflammation in the CNS, neuroinflammation, is not surprising, the CNS represents a unique structure-functional entity that requires special consideration for the understanding of the role of the IL-1 system in the brain. First, the presence of the blood-brain barrier (BBB) restricts the entry of many immune signal molecules and cells from easy access to the brain, preventing undesirable consequences of peripheral style of inflammation (swelling, for example) that could overwhelm the finite space of the brain; second, the presence of brain specific cell types-neurons, astrocytes, microglia, oligodendrocytes, ventricular ependymal cells, and choroid plexus cells-suggests IL-1 system may conduct neuroinflammation differently in this special environment through these cell types; third, recent studies have revealed that IL-1 can directly modulate neural circuitry and function and the subsequent neuroimmune crosstalk impacts neuroinflammation, neural function, and behavior, expanding the role of the IL-1 system into the realm of neurobiology. This mini-review summarizes the current state of knowledge about how the CNS IL-1 system might regulate neuroinflammation.