Sepsis is characterized by an uncontrolled inflammatory response to invading microorganisms. We describe the inflammatory mRNA profiles in whole-blood leukocytes, monocytes, and granulocytes using a multigene system for 35 inflammatory markers that included pro-and anti-inflammatory cytokines, chemokines, and signal transduction molecules in a case-control study with 34 patients with sepsis caused by the gram-negative bacterium Burkholderia pseudomallei (the pathogen causing melioidosis) and 32 healthy volunteers. Relative to healthy controls, patients with sepsis showed increased transcription of a whole array of inflammatory genes in peripheral blood leukocytes, granulocytes, and monocytes. Specific monocyte and granulocyte mRNA profiles were identified. Strong correlations were found between inflammatory mRNA expression levels in monocytes and clinical outcome. These data underline the notion that circulating leukocytes are an important source for inflammatory mediators in patients with gram-negative sepsis. Gene profiling such as was done here provides an excellent tool to obtain insight into the extent of inflammation activation in patients with severe infection.Melioidosis is caused by the gram-negative bacillus Burkholderia pseudomallei and is an important cause of severe sepsis in southeast Asia and northern Australia (4, 23). The most feared clinical picture is melioidosis septic shock, which is often associated with pneumonia, bacterial dissemination to distant sites, and a high mortality. Not surprisingly, melioidosis is regarded as an excellent model to study gram-negative sepsis (17): melioidosis is prevalent among rice farmers in southeast Asia (a relatively homogenous population) and is acquired in a community setting, patients present in large numbers to a single institution, and melioidosis is caused by a single organism and is associated with a high mortality rate.Sepsis is defined as the systemic inflammatory response to infection and is one of the leading causes of death in the western world (15). It has been well established that an uncontrolled activation of the inflammatory system in response to an invading pathogen can result in multiorgan failure and eventually death. Activation of leukocytes and activation of the cytokine and chemokine networks are prominent features of the septic response. However, knowledge about the nature of this acute inflammatory state and the role of circulating leukocytes is limited. Most studies on the role of inflammation in sepsis have focused on the plasma levels of inflammatory mediators, most notably cytokines. However, plasma protein levels do not fully reflect the inflammatory signature of leukocytes in whole blood. Furthermore, tissue leukocytes and parenchymal cells may contribute to the plasma levels of inflammatory mediators. To date, little work has been devoted to leukocyte mRNA expression profiles in patients with sepsis. Preliminary studies using real-time reverse transcription-PCR or gene arrays have suggested activation of multiple pathways in ...