Heat shock proteins 70/90 and associations with immunosuppression along with sepsis: preliminary data

Introduction

CD14/HLADR is an index of immune suppression. Heat shock proteins (hsp) regulate cell response to oxidative stress. We evaluated the relationship of CD14/HLADR and hsp70/90 in patients with SIRS and severe sepsis versus healthy volunteers.

Methods

We evaluated 31 patients with SIRS or severe sepsis against a group of sex-matched healthy volunteers. Demographic data were obtained for all patients. APACHE score was calculated upon admission. Blood samples were collected upon diagnosis of SIRS or severe sepsis. To evaluate the %HLA-DR expression on monocytes, the fresh whole blood was stained with anti-CD14-FITC, anti-HLA-DR-PE and CD45PC5 while staining with anti-CD33-PE, anti-CD45-PC7, anti-hsp70-FITC and anti-hsp90-PE allowed evaluation of the MFIexpression of hsps on CD33⁺ monocytes. Cells were then analyzed using flow cytometry. ANOVA with post hoc tests was used to compare CD14/HLADR cell counts and hsp70 and hsp90 levels among the three groups.

Results

Nineteen controls, six SIRS patients and 25 severe sepsis patients were studied. The percent expression of HLADR on CD14⁺ monocytes was significantly different between the three groups showing progressive decrease from controls (mean 90.5 ± 3.8%) to SIRS (mean 61.2 ± 5.9%) to severe sepsis (mean 39.2 ± 5.5%) patients (controls vs. severe sepsis, P < 0.001; controls vs. SIRS, P = 0.006; SIRS vs. severe sepsis, P = 0.03). hsp70 and hsp90 MFIwere significantly different between controls (mean 49.5 ± 4.9 and 33.5 ± 3.4 respectively), SIRS (mean 69.9 ± 16.5 and 46.5 ± 5.7 respectively) and severe sepsis patients (mean 33.3 ± 4.5 and 21.7 ± 2.7 respectively) (P < 0.05 for all comparisons). Notably, the hsp level rose from controls to SIRS and fell from SIRS to severe sepsis patients. APACHE score increased significantly (P = 0.023) in septic patients compared with SIRS.

Conclusion

There were a significant difference in CD14/HLADR, a marker of immune paralysis, between controls and patients with SIRS or severe sepsis. hsp70 and hsp90 showed an initial stimulation followed by exhaustion as sepsis progressed.

Acknowledgements

This research was co-financed by the European Union (European Social Fund) and Greek national funds through the Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Framework Research Funding Program: THALES. This abstract is part of the study 'Heat Shock Proteins and Glutamine Alterations Related to Hormonal, Immunological, Inflammatory and Molecular Response to Sepsis: A Combined Clinical and Experimental Study'.