Differential alterations in plasma colony-stimulating factor concentrations in meningococcaemia

Abstract

To determine whether circulating levels of any of the colony-stimulating factors (CSF) might contribute to the host response in severe sepsis, plasma concentrations of granulocyte CSF (G-CSF), granulocyte-macrophage CSF (GM-CSF), and macrophage CSF (M-CSF) were measured by immunoassays in 20 subjects with meningococcaemia, a bloodstream infection caused by Neisseria meningitidis, that has proven to be a valuable model to study the responses of other inflammatory mediators during sepsis and septic shock in humans. Plasma G-CSF concentrations were transiently elevated in most subjects during the early phase of meningococcaemia, and were higher in subjects with septic shock (mean ± s.d. = 165 ± 142 ng/ml, n = 9) compared with those who remained normotensive (mean ± s.d. = 7 ± 2 ng/ml, n = 10) (P < 0.05). Peak plasma G-CSF concentrations > 10 ng/ml were associated with the development of septic shock (P < 0.01), disseminated intravascular coagulation (P < 0.01 ), fulminant infection (P < 0.05), and a fatal outcome (P < 0.01). Plasma GM-CSF concentrations > 1 ng/ml were briefly present in subjects with life-threatening septic shock (1-15 ng/ml, n = 5), and were strongly associated with fulminant meningococcaemia (P < 0.01). Plasma M-CSF concentrations were marginally elevated in all subjects, but were not associated with complications related to or arising from sepsis-induced organ injury. This study demonstrates that plasma levels of G-CSF, GM-CSF and M-CSF show very different responses during meningococcaemia, changes which presumably reflect the different roles played by these mediators in sepsis and, potentially, in septic shock.