Resumen de Therapeutic role of il-37 after injury to the nervous system
Spinal cord injury (SCI) is one of the main causes of mortality among patients under 50 years old. It occurs in most countries at an annual rate of 20¿40 people per million of inhabitants, affecting more at men than women with a ratio of 4:1. Unlike peripheral nervous system (PNS), central nervous system (CNS) of adult mammals has limited abilities for spontaneous self-repair which leads to permanent functional deficits. This is due, in part, by: the poor intrinsic capacity of central neurons to regenerate their axons following injury, the limited ability of the CNS to replace dead neurons and oligodendrocytes, the inappropriate environment of the CNS to support axonal growth.
The pathophysiology of SCI involves two stages: the primary and the secondary injury. The first results from the mechanical trauma to the spinal cord that directly disrupts axons, blood vessels, membranes of neurons and glial cells, and myelin. This is followed by the secondary wave of tissue degeneration, which occurs over a period of several weeks, and encompasses a sequence of cellular and molecular events that are triggered in the spinal cord parenchyma as a result of the primary trauma. The mechanisms of secondary injury are multiple and not well defined, however a large number of studies indicates that inflammation is the main contributor to secondary injury.¿Inflammation is an essential aspect of the injury response and a means to curb infections and initiate wound healing. Chemokines and cytokines play an important role in the recruitment and activation of peripheral immune and CNS glial cells to initiate and maintain the inflammatory response. Regardless of the tissue in which it occurs, the inflammatory response is normally self-limiting and undergoes resolution in a timely fashion.
Although the inflammatory response is required for the clearance of cell and myelin debris and for wound healing in SCI, immune cells secrete several factors that cause damage to tissue. The damaging effects of inflammation are more pronounced in the CNS than other tissues because of the limited capacity of the CNS for axon regeneration and replenishment of damaged neurons and glial cells. Moreover, and in contrast to host tissues, inflammation does not terminate in a timely manner following SCI, leading to the development of chronic inflammation that further increase the degeneration of the spinal cord tissue.
IL-37, also known as IL-1 family 7b (IL-1F7) is an anti-inflammatory cytokine. IL-37 suppresses innate immune response by silencing the expression of pro-inflammatory cytokines without altering those that are anti- inflammatory. IL-37 might therefore be a suitable candidate to reduce inflammation and thus mediate protection and functional recovery after SCI. Moreover, IL-37 could potentially be used for other CNS and non-CNS disorders where the immune response plays a detrimental role such as acquired brain injury Alzheimer¿s disease, atherosclerosis, asthma and arthritis, among others.
