Changes In Immunological Response In Wistar Rats That Ingested Water From High And Low Disease Prevalent Areas From The North Central Province (NCP) And Low Disease Prevalent Colombo, Sri Lanka And Their Co-Relations To Histopathological Changes.

Abstract

BackgroundChronic Kidney Disease of unknown etiology (CKDu) is prevalent in North Central Province (NCP) of Sri Lanka and ingestion of ground water is identified as one of the causative factors. Majority of the population in the NCP consume un-boiled dug well water. Objective of this study was to find out the haematological and immunological variations in Wistar rats that ingested water from high and low disease prevalent areas from the NCP and low disease prevalent Colombo and correlated the findings with histopathological changes.Method Wistar rats (60) were recruited to the study and their baseline WBC, DC, CD4+, CD8+, serum cytokines, creatinine, ALT, AST and BUN levels were measured. Rats were randomly divided into 6 groups by assigning 10 rats into each group. Groups 1, 2 and 3 were given water from high disease prevalent New Town Medirigiriya (NTM), Bisobandaragama (BB) and Divuldamana (DD) and group 4 was given boiled water from NTM (NTMB). Group 5 and 6 were given water from low diseases prevalent Huruluwewa (HW) from NCP and low disease prevalent Colombo (CO). Serum cytokines (IL1ß, IL6, TNFα) were measured after 8 months and other parameters and tissue cytokines were measured after 14 months. Histopathology was performed in kidney and liver tissues.Results Serum TNFα levels were significantly elevated in rats from DD and BB but tissue TNFα levels were significantly elevated only in rats from DD. Rats from high diseases prevalent areas had significantly high CD4+ and CD8+ cell than those from low disease prevalent HW and CO. Immunological findings were correlated with the changes observed in the histopathology. There was a co-relation between the kidney Tubular Interstitial Lesion index and liver lesions.Conclusion TNFα and CD4+ and CD8+ lymphocyte had an impact on kidney damage. Rats with severe TI lesions reported high percentage of portal tracts and parenchymal lesions in the liver and this expression was minimum in CO. Boiled water can reduce the liver damage but not been able to significantly reduce the kidney damage. Immune therapy targeting the CD4+, CD8+ and TNFα may reduce the disease burden in the early stage.