High levels of circulating GM-CSF+CD4+ T cells are predictive of poor outcomes in sepsis patients: a prospective cohort study

Granulocyte colony-stimulating factor (GM-CSF), produced by CD4(+) T cells, has recently been implicated in the pathogenesis of inflammatory diseases, such as multiple sclerosis and juvenile arthritis. However, the role of GM-CSF-producing CD4(+) T cells in sepsis remains unknown. This study reports peripheral changes in GM-CSF-producing CD4(+) T cells in septic patients and the possible underlying mechanism by which GM-CSF influences the outcome of sepsis. Forty-three septic patients, 20 SIRS patients, and 20 healthy controls were enrolled in this study and followed for 28 days to assess mortality. We measured the peripheral frequency of GM-CSF(+)CD4(+) T cells and recorded their associated relationship with disease progression. Our data demonstrated that peripheral GM-CSF-producing CD4(+) T cells were significantly higher in septic patients than in both SIRS patients and healthy controls. These cells exhibit a memory phenotype and impaired IFN-gamma-secreting capacity in sepsis patients. Using a receiver operating curve analysis with 8.01% as a cut-off point, the percentage of GM-CSF(+)CD4(+) T cells could predict the outcome of septic patients. Combined with the increase in GM-CSF-producing CD4(+) T cells, inflammatory cytokines IL-1 beta and IL-6 were also upregulated. Using an in vitro neutrophil model, we found that GM-CSF inhibited C3aR expression, while inducing IL-8 production. Furthermore, this effect was transferrable in plasma from sepsis patients and was attenuated by inhibition of GM-CSF using an antiGM-CSF antibody. These results indicate that GM-CSF-producing CD4(+) T cells may serve as a marker of sepsis severity. Thus, targeting GM-CSF overproduction may benefit sepsis patients.