[Influence of gender on stimulated cytokine response in patients with severe sepsis].
OBJECTIVE
Studies suggest that female mice have lower mortality rates than males after sepsis or trauma-hemorrhage. This study investigated the impact of gender and disease severity on monocyte hyporesponsiveness in severe human sepsis.


METHODS
We prospectively investigated 49 (male n=28, female n=21) consecutive patients with severe sepsis. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were assayed by ELISA in unstimulated whole blood cultures or after stimulation with lipopolysaccharide (LPS; E. coli 0111:B4) or Staph. aureus Cowan strain I (SAC-I) lysate at days 1, 2, 3, 4, and 8 after enrollment. Testosterone and estradiol levels were quantified by electrochemoluminescence immunoassays.


RESULTS
Mortality was similar for males (35.7%) and females (42.9%). While disease severity was also comparable, septic patients showed a substantial suppression in stimulated TNF-alpha response compared to healthy controls who recovered within 8 days in surviving patients. Stimulated cytokine response recovered in female non-surviving patients, while it remained suppressed in non-surviving male patients and was significantly different compared to female non-surviving patients. Testosterone levels were substantially suppressed in male but not female septic patients compared to normal values but did not differ between surviving and non-surviving patients. Estradiol levels were elevated in female and male septic patients. Addition of different concentrations of testosterone and estradiol to whole blood obtained from younger (<35 years old) and older (>60 years old) male as well as from younger (proestrous premenopausal) and older (postmenopausal) female non-septic volunteers revealed no effect on LPS-stimulated TNF-alpha and IL-10 release.


CONCLUSIONS
Severe sepsis leads to a substantial suppression of stimulated cytokine response. Prolonged suppression may serve as a marker of unfavourable outcome in male but not in female individuals suffering from severe sepsis. Furthermore, our data suggest that gender differences in cellular immunity described for young, sexually mature animals obviously persist in typical postmenopausal intensive care unit patients, although a direct interaction between testosterone or estradiol and LPS-stimulated cytokine response could not be demonstrated.
Bauer
I
I
Klinik für Anaesthesiologie, Intensivmedizin und Schmerztherapie, Universität des Saarlandes, Homburg, Germany. aiibau@uniklinik-saarland.de
Bauer
M
M
Raddatz
A
A
Luedtke
C
C
Werth
M
M
Silomon
M
M
Rensing
H
H
Wilhelm
W
W
D018806:APACHE; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011446:Prospective Studies; D018805:Sepsis / Q000378:metabolism* / Q000401:mortality; D012727:Sex Characteristics; D013268:Stimulation, Chemical; D016019:Survival Analysis; D013739:Testosterone / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013739:Testosterone; D004958:Estradiol