The Potential Role of Thrombopoietin and Interleukin-6 in the Thrombocytosis Effect of Carica papaya Leaves

Abstract

Dengue fever is endemic in tropical urban developing regions worldwide. Thrombocytopenia is an important clinical feature which may result in bleeding. However, there is no specific treatment for Dengue-induced thrombocytopenia. Carica papaya leaves (CPL) is a popular remedy in South East Asia to treat Dengue-induced thrombocytopenia. Development of CPL into pharmaceutical therapeutic agents is not forthcoming due to lack of rigorous scientific evidence and unknown mechanism of action. This study investigated the role of thrombopoietin (TPO) and interleukin (IL-6) in the thrombocytosis effect of CPL in vivo. These experiments were conducted using busulfan-induced thrombocytopenic rats. Treatment of aqueous and methanol extracts of CPL at 600mg/kg were administered orally for 7 consecutive days and serum platelet count was determined intermittently until day 15. At the end of experiments, serum Thrombopoietin (TPO) and IL-6 levels were determined by ELISA. Both aqueous and methanol extracts of CPL significantly increased platelet count compared to the control groups (x2 (2) = 25.373, P = 0.00). Investigations into the mechanism of thrombocytosis showed that TPO and IL-6 levels were increased compared to controls but was not statistically significant (H (3) = 5.339 P = 0.149) (H (3) = 4.412 P = 0.220) respectively. This study is the  first to document the thrombocytosis effect of both aqueous and methanol CPL extracts in a rodent model system. Our findings showed that aqueous extract of CPL demonstrated an increase of TPO and IL-6 levels. We suggested that the possible mechanism could be linked with the upregulation of major thrombopoietic cytokines such as TPO and IL-6.