P1139EXPRESSION OF TOLL LIKE RECEPTORS, CELL ADHESION MOLECULES AND PRO-INFLAMMATORY CYTOKINES IN ESRD PATIENTS

Abstract

Abstract Background and Aims CAPD is well established modality of treatment for patients with end stage renal disease (ESRD). Peritonitis is a leading cause of technique failure and death in patients on CAPD. Studies on expressions of host factors like TLRs, CAMs and their relationship with inflammatory cytokines (IL-6, IL-12, TNF-alpha and IL-1 beta) involved in peritonitis and other co-morbidity and functional status are lacking throughout the world. Hence the present study has to be done to determine the expressions of TLR2 and TLR4, and CAMs in ESRD patients. To compare the expression of TLR2, TLR4, ICAM 1 and Pro-inflammatory cytokines (IL-6, IL-12, TNF-alpha and IL-1-beta) in Peritonitis, CAPD and CRF group patients. Method A total of 85 ESRD patients recruited and sub-divided into 3 groups. Group1- CAPD patient (n=25), Group 2- Peritonitis patient (n=30), and Group 3- CRF (n=30 patients). mRNA expression of TLR-2, TLR-4 were examined at gene levels by RT PCR and cell adhesion molecule (ICAM-1) were examined at gene and protein levels by RT PCR and ELISA respectively in Serum and Pro-inflammatory cytokines level were also examined by ELISA in serum. We performed microbiological culture for bacterial and fungal pathogens using automated BACTEC culture system. Cell counts were routinely done on every dialysate. Results Out of 30 samples of peritonitis group 15 were culture positive and 15 were culture negative. We found that in peritonitis group the mRNA expression of TLR-2 and TLR-4 was higher as compared to CRF (4.183±2.857vs 3.633±2.41) (p=0.049), (4.314±2.91vs 4.14±1.99) (p=0.015) and CAPD (4.183±2.857vs3.683±2.85) (p=0.041), (4.314±2.91vs 3.88±1.91) (p=0.009) respectively. At gene and protein level ICAM-1 was higher in peritonitis patient compared to CAPD (mRNA expression 4.76±2.64vs 4.36±3.48) (level in sera 660±201.2vs 514±157) (p=0.003). The IL-6 and IL-12 expression was higher in Peritonitis group as compared to CAPD (66.87±64.51vs214.35±220.05) (p=0.04) and (230.17±153.45vs417.04±302.96) (p=0.028) respectively. The TNF-alpha and IL-1-beta expression was not significant among the groups. Conclusion TLRs activation by bacterial molecules leads to the induction of cytokines (IL-6 and IL-12) and chemokine through the activation of NF-ķB pathway and may be responsible for atherosclerosis, morbidity and mortality in ESRD patients. Elevated level of ICAM-1, IL-6 and IL-12 may be responsible for chronic inflammation in Peritonitis group patients.