Thesis Abstract

Abstract
Lymphatic filariasis caused by Wuchereria bancrofti is a debilitating disease affecting millions of people in tropical and subtropical regions. The immune response to the parasite plays a crucial role in the pathogenesis of the disease. Kolaviron, a natural biflavonoid complex derived from Garcinia kola seeds, has been reported to possess various biological activities including antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of kolaviron on lymphocyte proliferation, expression of toll-like receptor 2 (TLR2), and vascular endothelial growth factor-C (VEGF-C) genes in W. bancrofti-infected blood. Peripheral blood mononuclear cells (PBMCs) were isolated from W. bancrofti-infected individuals and treated with different concentrations of kolaviron. Cell proliferation was assessed using the MTT assay, and gene expression levels of TLR2 and VEGF-C were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that kolaviron significantly inhibited lymphocyte proliferation in a dose-dependent manner. Furthermore, kolaviron downregulated the expression of TLR2 and VEGF-C genes in PBMCs from W. bancrofti-infected individuals. These findings suggest that kolaviron may modulate the immune response in W. bancrofti infection by suppressing lymphocyte proliferation and downregulating the expression of TLR2 and VEGF-C genes. Further studies are warranted to elucidate the underlying mechanisms of kolaviron action and its potential as an adjunct therapy for lymphatic filariasis.

Thesis 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).