In addition to passive release from necrotic cells, HMGB1 can be secreted actively by inflammatory cells (monocytes, macrophages, dendritic cells, etc.). A number of viral illnesses including SARS and influenza result in the elevation of proinflammatory cytokines (TNF, IL-1, IL-6, types I and II interferon) that could be responsible for inducing release of HMGB1 from inflammatory cells, thus leading to the propagation of the immune response (36) .