CD64 upregulation on peripheral granulocytes is not a marker of sepsis and does not correlate with serum concentrations of granulocyte colony-stimulating factor (G-CSF) in postoperative/posttraumatic patients with severe sepsis

Purpose

To study whether the modulation of the expression of CD64 on the surface of neutrophils correlates with the inflammatory response and changes in serum concentrations of G-CSF in postoperative/posttraumatic patients with severe sepsis and septic shock.

Methods

Sixteen of these patients were studied upon admission to the intensive care unit (ICU) staying for more than 5 days. In these patients, a longitudinal analysis on the kinetics of leukocyte counts, the expression of CD64 and G-CSF serum concentrations was performed on a daily basis until discharge from the ICU. Surface expression was tested by flow cytometry using a Coulter Epics XL-MCL (Coulter Electronis, Krefeld, Germany). Results are expressed as a ratio between the mean channel value of the CD64-positive granulocyte fraction and the isotype control IgG₁, ie CD64/IgG₁.

Results

In all patients, CD64 was homogeneously expressed on all granulocytes. Six out of the 16 patients responded with an increase in CD64/IgG₁ > 2.5 following manifestation of an infectious focus. In the remaining 10 patients CD64/IgG₁ remained or declined below 2.5 and even below 1.5 despite bacterial infection, severe sepsis and septic shock. High expression of CD64-density (ratio > 2.5) occured incidentally with low serum concentrations of G-CSF (< 170 pg/ml) in individual patients and vice versa, i. e., low CD64 ratio < 1.5 and high G-CSF (up to 65,000 pg/ml). In a single patient with shock not due to infection, CD64/IgG₁ remained below 1.7, despite serum concentrations of G-CSF up to 2300 pg/ml. Serum concentrations of G-CSF did not correlate with the expression of CD64 (r = 0.02–0.61 for individual patients).

Conclusions

G-CSF has been proven a relevant hematopoietic factor to cope with acute inflammation and sepsis in vivo. CD64 expression has been suggested to indicate G-CSF serum activity and activation of neutrophils in vivo, and to serve as a marker of sepsis. The non-responsiveness of CD64 to G-CSF indicates that other factors must be involved and that active counterregulatory effects occur in patients with severe sepsis and septic shock. Thus, CD64 expression cannot serve as a longterm marker of sepsis.