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HMGB1 is an early mediator in sterile injury and a late mediator in infection. Infection activates innate immune cells to produce HMGB1, which occurs after a significant lag, placing it downstream of an early TNF response. During ischemia and other forms of sterile cell injury, HMGB1 is released as an early mediator that in turn activates the later release of TNF and other cytokines.
