Reduced capacity of mononuclear cells to synthesize cytokines against an inflammatory stimulus in uremic patients.
BACKGROUND
The local production of cytokines and phagocytosis is pivotal in innate immunity. Uremic patients have a high infectious morbidity, but it remains unclear if this arises from incompetence of these local cellular functions.


METHODS
In 30 predialysis uremic patients and 20 controls, we studied the intracellular cytokine synthesis by mononuclear cells in response to stimulation. Moreover, phagocytic activity by leukocytes was tested. Lipopolysaccharide- or mitogen-stimulated peripheral blood cells were labeled with anti-CD14 and -CD4 antibodies, respectively and subjected to intracellular cytokine staining and flow cytometry. Tumor necrosis factor (TNF)-alpha, IL-1beta, IL-6, and IL-8 synthesis was examined in CD14(+) monocytes. IFN-gamma and IL-4 synthesis was examined in CD4(+) helper T cells to determine their Th1 or Th2 phenotype. The flow cytometric analysis of phagocytosis of opsonized bacteria was performed in whole blood.


RESULTS
Uremic patients exhibited a significantly reduced monokine response and inhibited development of helper T cells into Th1 or Th2 phenotypes compared with control subjects. Their phagocytic activity was comparable to control subjects. No clinical parameters were linked to in vitro cytokine production and phagocytic activity.


CONCLUSIONS
Mononuclear cells in uremic patients are hyporeactive to inflammatory challenge and this may be one reason why uremic patients are vulnerable to infections.
Ando
Minoru
M
Department of Nephrology, Tokyo Metropolitan Komagome Hospital, Bunkyo-Ku, Tokyo, 113-8677 Japan. nephrol@cick.jp
Shibuya
Asuka
A
Tsuchiya
Ken
K
Akiba
Takashi
T
Nitta
Kosaku
K
D001419:Bacteria; D016764:Cell Polarity; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000139:chemically induced; D007425:Intracellular Membranes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology*; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D010641:Phenotype; D013194:Staining and Labeling; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells; D018418:Th2 Cells; D014511:Uremia / Q000097:blood* / Q000276:immunology / Q000503:physiopathology
D016207:Cytokines; D008070:Lipopolysaccharides; D008934:Mitogens