Cytokines and peritonitis in continuous ambulatory peritoneal dialysis: immunodeviation and immunodeficiency

Cytokines are soluble mediators of the immune system, which regulate the immune response to antigenic stimuli. In continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis, an inflammatory process occurs, but the patterns of cytokine secretion have not yet been clarified. We compared the characteristics of the intracellular production of cytokines and looked for the immunophenotypes T helper 1 (TH1), T helper 2 (TH2), and T helper 0 (TH0) in CAPD patients with and without peritonitis. Our descriptive, prospective study was carried out in the dialysis unit of the San José University Hospital, a tertiary health care center in Popayán, southwest Colombia. We obtained 28 peripheral blood samples from CAPD patients (8 with peritonitis and 20 without peritonitis) and processed them by flow cytometry for intracellular detection of cytokines. The peritonitis diagnosis was made based using established clinical and laboratory criteria. We measured the general clinical characteristics and percentage of intracellular production of interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-12 (IL-12), tumor necrosis factor alpha (TNF alpha), interleukin-4 (IL-4), and interferon-gamma (INF-gamma) in T lymphocytes. Diabetic nephropathy and chronic glomerulonephritis were the most frequent primary pathologies in both groups of patients. The patients on CAPD without peritonitis expressed high levels of CD69 and the pro-inflammatory cytokines IL-1, IL-6, IL-12, TNF alpha, and IL-4, indicating in vivo immune activation similar to the group with peritonitis. In the group without peritonitis, 95% of samples displayed immunodeviation TH2. Just 5% of samples approached TH0, producing IFN-gamma. After mitogen activation, 45% of the samples stayed in TH2; 55% approached TH0. Patients with peritonitis produced high levels of IL-4 and little IFN-gamma, which indicates immunodeviation TH2 in 75% of samples; 25% approached TH0. When cells were stimulated by ionomicin and phorbol 12-myristate 13-acetate (PMA), more IFN-gamma appeared and high levels of IL-4 persisted in 75% of the samples, which looked like intent to correct the TH2 immunodeviation toward TH0. Patients on CAPD with and without peritonitis showed immune activation per se and high production of pro-inflammatory cytokines accompanied by a strong pattern of cytokine TH2 and a deficiency of IFN-gamma production, suggesting heavy immunodeviation TH2 and immunodeficiency TH1 (owing to the deficit of IFN-gamma). Finally, with in vitro immune stimulation, the TH2 pattern tried to approach TH0.