[Innate immunity in hemodialysis and continuous ambulatory peritoneal dialysis patients: impaired cytokine synthetic response to ex-vivo stimuli in mononuclear cells].
Dialysis patients are weak in immune host defense, which is associated with their high morbidity of infection. Polymorphonuclear leukocytes (PMNLs) and mononuclear cells play a key role in innate host defense. PMNLs and monocytes have bactericidal activity through the process of phagocytosis. Monocytes and lymphocytes contribute to the development of innate immunity by their cytokine actions. We studied the intracellular cytokine syntheses in response to ex-vivo stimuli, which may reflect the potential reactivity of immune cells in cytokine syntheses when pathogens invade humans. Furthermore, phagocytic activity was assessed in granulocytes and monocytes. Twenty HD, 15 CAPD, and 10 age-matched controls were enrolled in this study. One milliliter of whole blood from each subject was incubated with lipopolysaccharides (LPS) or mitogens for 4 hours at 37 degrees C. Monoclonal antibodies to CD14+ and CD4+ were used for identifying monocytes and helper T cells, respectively. Intracellular cytokines were stained using FASTIMMUNE staining kits. Interleukin-1beta and TNF-alpha syntheses were examined in monocytes, which are the most important early-response cytokines in innate immunity. IFN-gamma and IL-4 syntheses were examined in helper T cells to observe their polarization into Th1 and Th2 cells. IFN-gamma is a key factor in establishing innate immunity. The percentage of cells that stained positive for each cytokine was analyzed using a flow cytometer. The following results were obtained: 1) In CAPD patients, IL-1beta and TNF-alpha response to LPS in monocytes were significantly reduced, as compared to other subjects. Polarization of helper T cells was reduced, resulting in a significant decrease in Th1 cells. 2) In HD patients, monokine responses were not altered, but polarization of helper T cells was skewed toward a Th1 type. Phagocytic activities were not impaired in both dialysis groups. In conclusion, mononuclear cells from CAPD patients have the potential to exhibit failure of a cytokine response to ex-vivo stimuli in terms of innate immunity.
Shibuya
Asuka
A
Department of Medicine IV, Tokyo Women's Medical University, Japan.
Ando
Minoru
M
Tsuchiya
Ken
K
Akiba
Takashi
T
Nihei
Hiroshi
H
D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010587:Phagocytosis; D006435:Renal Dialysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D016207:Cytokines