Time course of granulocyte–macrophage colony-stimulating factor and IL-8 in severe sepsis: are the initial low levels of IL-8 a consequence of immunodepression?

Background

Neutrophil proliferation, activation and recruitment are key events in the pathogenesis of sepsis. Granulocyte–macrophage colony-stimulating factor (GM-CSF) and IL-8 are cytokines regulating the proliferation, differentiation and maturation of polymorphonuclear cells and mononuclear phagocytic progenitors, enhancing their functions, adhesion and chemotaxis.

Materials and methods

In 11 patients fulfilling the ACCP/SCCM criteria for severe sepsis, we analyzed serum levels of GM-CSF and IL-8 at days 1, 2 and 7 after admission. Patients (10 males/one female) had a median age of 68 years (range 22–87 years). The primary infection had urinary (seven patients) and respiratory (four patients) origins. Seven healthy volunteers served as controls.

Results

Four out of 11 patients had positive blood cultures (Gram-negative). At admission, the median procalcitonin was 2 ng/ml (0.5–10 ng/ml). All patients survived except one patient that died 5 days after admission following acute myocardial infarction. GM-CSF was always below the detection limit (7.8 pg/ml) in septic patients and controls. In seven patients, serum IL-8 was below the detection limit (31.2 pg/ml) at all time points. The median value for IL-8 for the group of patients was 0 pg/ml (0–264 pg/ml), but while IL-8 was absent in the sepsis of respiratory origin it had a median value of 32 pg/ml in urinary sepsis. Surprisingly, IL-8 was detectable in five out of seven controls, with a median of 68.7 pg/ml (0–145.2 pg/ml).

Conclusion

We failed to identify detectable circulating levels of GM-CSF in healthy individuals or in severe sepsis. The circulating levels of IL-8 were lower in septic patients than in healthy controls. As previously suggested, locally produced GM-CSF might have a role in this condition. Initial low levels of IL-8 found might be a component of the immunodepression seen in severe sepsis. Also, it is possible that the IL-8 levels correlate with the primary site of infection and the severity of the immunodepression related to that.