Interleukin 33 (IL33) as a Potential Immunotherapeutic Target in Malaria

Abstract

Malaria is a prevalent, multi-species parasitic disease that causes both significant global health and economic problems. Efforts in eradicating and treating it has been dampened by many obstacles in vaccine development, drug resistance and vector resistance towards insecticides. In this study, we aimed at investigating the potential of targetting IL33 for immunotherapeutic development in malaria infection. IL33 is a dynamic molecule that exists either as intracellular or extracellular cytokine and acting either as pro or antiinflammatory mediator in various diseases. Plasmodium berghei ANKA infection in ICR mice was used as a model of malaria. The local and systemic release of IL33 were determined during the infection followed by the effects of modulating IL33 levels on the survival rate and histopathological features of major organs in malaria infected mice. The modulating stratergy was carried out by neutralizing and antagonizing IL33 using monoclonal antibody and chimera protein respectively, or by augmenting IL33 using recombinant protein. Results showed that IL33 was significantly elevated in the plasma during the infection and significant positive correlation between the elevated IL33 levels and parasitaemia development was also observed. Immunohistochemical analysis revealed significant local expression of IL33 in the brain, lung and spleen tissues. Augmentation of IL33 levels systemically exhibited better survival rate and improved the severe histopathological features of various organs in malarial mice, whereas antagonizing and neutralizing IL33 levels produced lower survival rate and worsened histopathological features in malarial mice. Results obtained is highly indicative of the crucial role of IL33 during the infection and its potential to be a target for immunotherapeutic drug development for malaria infection.