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C5a receptor expression on leukocytes from patients with severe sepsis or septic shock

Background

Recently animal studies have been presented suggesting that complement factor C5a blockade might be of benefit in patients with severe sepsis/septic shock. In one study the expression of the C5a receptor (CD88) on the granulocytes from septic animals was increased. The aim of the present investigation was to study the CD 88 expression on leukocytes in human sepsis.

Methods

Twelve ICU patients fulfilling the ACCP/SCCM criteria for severe sepsis/septic shock were prospectively included into the study as early as possible in their septic course. Blood samples for analyses of leukocyte receptor expression and complement factors were taken on day 1, 3 and 15. The leukocytes were isolated from heparinised whole blood and labelled with CD88 antibodies. As controls leukocytes from 20 healthy individuals were used. The samples were analysed by the use of flow cytometry and results presented as mean fluorescence intensity (MFI). The complement proteins C3a and terminal complement complex (TCC) were analysed in EDTA plasma by capture ELISA techniques. Levels of TNF-α, IL-6, IL-8, IL-10, IL-1ra, and MCP-1 were analysed in EDTA plasma with ELISA technique.

Results

On day 1 10/11 patients had increased levels of C3a, 1144 ± 138 ng/ml, (mean ± SE) (normal range: 92–268) and 11/11 of TCC 146 ± 46 AU/ml (normal range: 12–56). CD88 expression on the granulocytes in the control group was 63 ± 4. In comparison with the controls, the patients with severe sepsis/septic shock had significantly lowered values: on day 1 37± 5 (P < 0.001), on day 3 45 ± 8 (P < 0.05), and on day 15 51± 8 (P < 0.05). The granulocyte expression of CD88 on day 1 correlated negatively to APACHE-II score at inclusion (r = -0.59, P < 0.05). Besides a weak correlation to IL-1ra, there were no significant correlations to the other cytokines. In the patient group, the CD88 expression on the monocytes did not change during the observation time and did not differ from that in the control group.

Conclusion

Although a transient increase at an earlier stage of the septic course cannot be excluded, our results demonstrate that the expression of the C5a receptor on granulocytes — at the time when diagnosis can clinically be made — is low, despite an activation of the complement system. Our result suggest that C5a blockade in human sepsis might be of a more limited value than that found in animal experiments.

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Furebring, M., Håkansson, L., Venge, P. et al. C5a receptor expression on leukocytes from patients with severe sepsis or septic shock. Crit Care 5, P065 (2001). https://doi.org/10.1186/cc1132

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Keywords

  • Septic Shock
  • Severe Sepsis
  • CD88 Expression
  • Receptor Expression
  • Mean Fluorescence Intensity