Sex differences in cytokine production and surface antigen expression of peripheral blood mononuclear cells after surgery.
BACKGROUND
Several clinical and epidemiological studies have observed a better outcome after sepsis in women than in men. The purpose of this study was to determine if these sex differences are observed in cytokine responses and the surface antigen expression of monocytes. In addition, the clinical courses of male and female patients after gastrointestinal surgery were compared.


METHODS
A total of 25 patients with gastric carcinoma who underwent gastrectomy were enrolled in this study. Tumor necrosis factor-alpha (TNF-alpha), interleukin-10, and interferon-gamma (IFN-gamma) production by lipopolysaccharide-stimulated peripheral blood mononuclear cells (PBMCs) as well as the expression of Toll-like receptor-4 (TLR-4), TLR-2, human leukocyte antigen-D related (HLA-DR), and CD16 on monocytes in 16 men and 9 women on the day before surgery were compared with measurements on postoperative day (POD) 1. Furthermore, postoperative infectious complications, the development of systemic inflammatory response syndrome, and serum C-reactive protein levels on POD3 were compared.


RESULTS
TNF-alpha production of PBMCs and TLR-2 and CD16 expression on monocytes were significantly higher in women than in men before surgery. IFN-gamma production of PBMCs and HLA-DR expression on monocytes were significantly lower in men than in women on POD1. Furthermore, TNF-alpha production of PBMCs on POD1 was significantly increased, and both IFN-gamma production and HLA-DR expression were significantly decreased compared with that observed before surgery in men, but no corresponding significant changes were observed in women. In addition, C-reactive protein levels on POD3 were significantly higher in men than in women.


CONCLUSIONS
Both TNF-alpha and interleukin-10 production of PBMCs and both TLR-2 and CD16 expression on monocytes were significantly higher in women than in men on the day before surgery. Excessive TNF-alpha and suppressive IFN-gamma production of PBMCs, as well as a decrease in HLA-DR expression on monocytes, occurred more often in men than in women after surgery, suggesting that these factors all contribute to an increased susceptibility of men to develop systemic inflammatory response syndrome or postoperative infectious complications.
Ono
Satoshi
S
Department of Surgery I, National Defense Medical College Research Institute, Namiki 3-2, Tokorozawa, Saitama, 359-8513, Japan. satoshi@ndmc.ac.jp
Tsujimoto
Hironori
H
Hiraki
Shu-Ichi
S
Takahata
Risa
R
Kinoshita
Manabu
M
Mochizuki
Hidetaka
H
D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004198:Disease Susceptibility; D005260:Female; D005743:Gastrectomy / Q000009:adverse effects*; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007564:Japan / Q000453:epidemiology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology / Q000276:immunology; D011956:Receptors, Cell Surface / Q000097:blood; D017452:Receptors, IgG / Q000097:blood; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000276:immunology / Q000601:surgery; D013312:Stress, Physiological / Q000209:etiology / Q000276:immunology*; D018746:Systemic Inflammatory Response Syndrome / Q000453:epidemiology / Q000276:immunology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000954:Antigens, Surface; D016207:Cytokines; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma