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.


CONCLUSIONS
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.
Wang
Hsin-Hui
HH
Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Lin
Ching-Yuang
CY
D000328:Adult; D001202:Ascitic Fluid / Q000737:chemistry* / Q000166:cytology; D002511:Cephalosporins / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D005260:Female; D050990:GATA3 Transcription Factor; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics; D018664:Interleukin-12 / Q000032:analysis*; D020382:Interleukin-18 / Q000032:analysis*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects; D010538:Peritonitis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020825:T-Box Domain Proteins; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D017334:Teicoplanin / Q000627:therapeutic use; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D000098815:T-bet Transcription Factor
D002511:Cephalosporins; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D020382:Interleukin-18; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D018664:Interleukin-12; D017334:Teicoplanin; D007371:Interferon-gamma