Free Heme Promotes Severe Sepsis

Blood’s iron-toting compound, heme, plays a central role in the development of severe sepsis, an extreme systemic inflammatory response to infection, Portuguese and Brazilian researchers report (Sci. Transl. Med. 2010, 2, 51ra71). Miguel P. Soares of the Gulbenkian Institute of Science, in Oeiras, Portugal, and coworkers discovered that free heme released from hemoglobin as a result of an infection promotes tissue damage and severe sepsis. Protoporphyrin IX—heme’s organic framework—doesn’t cause sepsis on its own, they note, but iron-containing heme can induce sepsis in mice with otherwise nonlethal infections. Liver cells that are exposed to free heme in combination with other cytotoxic agents undergo cell death that doesn’t happen in the presence of either the heme or the cytotoxic agents alone. The enzyme heme oxygenase-1, which catalyzes the breakdown of heme, prevents heme from inducing sepsis. In addition, the presence in plasma of hemopexin, a heme-sequestering protein, reduces heme’s damaging effects. The researchers found that the concentration of hemopexin in plasma can be used to predict the outcome of septic shock in patients, thereby leading the team to suggest that hemopexin could be used to treat severe sepsis.