EFFECTS OF KOLAVIRON ON LYMPHOCYTES PROLIFERATION, EXPRESSION OF TOLL LIKE RECEPTOR-2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR-C GENES IN WUCHERERIA BANCROFTI INFECTED BLOOD

EFFECTS OF KOLAVIRON ON LYMPHOCYTES PROLIFERATION, EXPRESSION OF TOLL LIKE RECEPTOR-2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR-C GENES IN Wuchereria bancrofti INFECTED BLOOD

CHAPTER ONE

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).

The World Health Organization (WHO) initiated the Global Programme to Eliminate Lymphatic Filariasis with the goal to eradicate lymphatic filariasis in endemic countries. This initiative utilizes Mass Drug administration, where Diethylcarbamazine, Albendazole or Ivermectin is administered mass treatment of lymphatic filariasis annually in endemic areas (WHO, 2013). These drugs have been proven not to have good macrofilaricidal efficacy and reported resistance developed by the parasites against the drugs (resistance associated mutation at Tyrosine codon 200 of β tubulin of parasite in albendazole treatment) and they do not alleviate the pathology of the disease ( Schwab et al., 2005; Hoerauf et al., 2011).

Recently, doxycycline a broad spectrum anti-biotic from the tetracycline family has been used on a single daily dose of 200mg for six weeks in the treatment of Bancroftian filariasis. The treatment resulted in the reduction of plasma vascular endothelial growth factors ( Hoerauf, 2008; Bennuru et al., 2010), hence the need to use it as our positive control in this study.

Kolaviron is found in defatted ethanol extract of Garcinia kola. The extract is one of the numerous plant products that have been found to have a wide range of medicinal value which include anti-diabetic, anti-inflammatory and anti-proliferative effects amongst other ( Farombi and Owoeye, 2011; Ayepola et al., 2014).

EFFECTS OF KOLAVIRON ON LYMPHOCYTES PROLIFERATION, EXPRESSION OF TOLL LIKE RECEPTOR-2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR-C GENES IN Wuchereria bancrofti INFECTED BLOOD