Interleukin-12 and -18 levels in peritoneal dialysate effluent correlate with the outcome of peritonitis in patients undergoing peritoneal dialysis: implications for the Type I/Type II T-cell immune response.

BACKGROUND: We previously showed that a positive impact of peritoneal defense response on the outcome of peritoneal dialysis (PD)-related peritonitis is characterized by an increased pattern of peritoneal CD4/CD8 T-cell ratio with a predominant CD4(+)-T helper subtype 1 phenotype. To further explore longitudinal changes in peritoneal immunity during PD-related peritonitis, we examined the production of interleukin 12 (IL-12), IL-18, and interferon gamma (IFN-gamma) in peritoneal dialysate effluent (PDE) and kinetic expression of the transcription factors T box expressed in T cells (T-bet) and guanine adenine thymine adenine (GATA) binding protein 3 (GATA-3) in peritoneal T cells during peritonitis. Correlations between these observations and responses to antibiotics were analyzed.
METHODS: IL-12, IL-18, and IFN-gamma protein and IFN-gamma, T-bet, and GATA-3 messenger RNA (mRNA) were measured in PDE during various phases of peritonitis in 40 patients undergoing PD. Patients were divided into 2 groups according to whether they had a rapid versus delayed response to antibiotic treatment.
RESULTS: In the early phase of peritonitis, IL-12, IL-18, and IFN-gamma levels in PDE were significantly greater in the rapid-response group (P < 0.05). Changes in peritoneal IL-12 and IL-18 levels preceded changes in IFN-gamma levels. The kinetics of IFN-gamma, T-bet, and GATA-3 mRNA expression in peritoneal T cells, measured by means of real-time polymerase chain reaction, differed between the 2 groups. In the rapid-response group, IFN-gamma and T-bet mRNA expression increased, whereas that of GATA-3 decreased over time. Results were opposite in the delayed-response group, with IFN-gamma and T-bet levels decreasing and GATA-3 levels increasing over time.
CONCLUSION: These data suggest that local IL-12 and IL-18 production is part of a protective early immune response to PD-related peritonitis. High IL-12 and IL-18 levels in PDE during the early phase of peritonitis correlated with a predominant type 1 immune response and favorable outcome.