Project Abstract

Abstract
The aim of this study was to investigate the effects of kolaviron on lymphocyte proliferation, expression of toll-like receptor-2 (TLR-2), and vascular endothelial growth factor-C (VEGF-C) genes in Wuchereria bancrofti-infected blood. Lymphatic filariasis caused by Wuchereria bancrofti is a major public health concern in tropical and subtropical regions. Kolaviron, a natural biflavonoid complex from Garcinia kola seeds, has been reported to possess immunomodulatory and anti-inflammatory properties. Peripheral blood samples were collected from individuals infected with W. bancrofti and treated with kolaviron. Lymphocytes were isolated and cultured in the presence of kolaviron, and cell proliferation was assessed using MTT assay. The expression levels of TLR-2 and VEGF-C genes were analyzed by quantitative real-time polymerase chain reaction (qPCR). The results showed that kolaviron treatment significantly inhibited lymphocyte proliferation in W. bancrofti-infected blood samples compared to untreated samples. Additionally, kolaviron downregulated the expression of TLR-2 and VEGF-C genes in lymphocytes from infected individuals. These findings suggest that kolaviron may modulate the immune response in W. bancrofti infection by suppressing lymphocyte proliferation and regulating the expression of TLR-2 and VEGF-C genes. Overall, this study provides insights into the potential immunomodulatory effects of kolaviron in lymphatic filariasis and highlights its potential as a therapeutic agent for the management of W. bancrofti infection. Further investigations are warranted to elucidate the underlying mechanisms of kolaviron action on lymphocytes and its impact on the host immune response to filarial parasites.

Project Overview

1.0 INTRODUCTION

Lymphatic filariasis, caused by parasitic Wuchereria bancrofti, is a mosquito borne disease characterized by a broad spectrum of clinical manifestation such as temporal/permanent disability and disfiguring leading to severe damage and painful swellings (lymphedema) of the legs and genitals in the late stage of the disease (Hoerauf et al., 2011; WHO, 2012; Gomase et al., 2013) and eventually stigmatization (WHO, 2013). Although the events leading to the development of chronic pathology in lymphatic filariasis are not fully understood, live filarial parasite and/or their products have a direct effect on lymphatic endothelial cells and in the cells of the innate and adaptive immune system (Nutman, 2013). Vascular endothelial growth factor (VEGF) family which is key regulators of endothelial cell functions has been implicated in lymphangiogenesis and angiogenesis in lymphatic pathology (Pfar et al., 2009). Their levels are significantly elevated in individuals with filarial infection both in chronic and microfilaremic states (Bennuru et al., 2010). The key mediators when it comes to complications associated with lymphatic filariasis are toll like receptors (TLR). They are pattern recognition factors of the innate immune system responsible for the microbial detection and initiation of the host immune response (Kawai and Akira, 2010). Wolbachia, a Gram negative endosymbiont in filarial parasites are key inducers of pro inflammatory cytokines which interact with the immune system through TLR2 thus, contributing to the pathology of lymphatic filariasis (Hise et al, 2007).