Parasite load and plasma cytokine levels in Trypanosoma Brucei infected rats administered with systemic IL-6 AND IL-10

Abstract

The invasion of central nervous system (CNS) by trypanosomes is mediated by cytokine modulations and responses. The pro-inflammatory cytokine response facilitates the progression to the late stage while the anti-inflammatory cytokine responses hinder this progression. The study assessed parasite load and selected plasma cytokine levels in Trypanosoma brucei brucei infected rats administered with systemic IL-6 and IL-10 for novel therapeutic agent development. Wister albino rats were infected with Trypanosoma brucei brucei GVR35 and then administered with IL-6, IL- 10 or combined IL-6 and IL-10 on day 11 post-infection. Monitoring of blood trypanosome density from day 11-17 post-infection was by microscopy. Trypanosome density in CNS was determined by real-time quantitative PCR for trypanosome Pfr2 gene copies. Plasma cytokine levels were measured by sandwich Enzyme-Linked Immuno Sorbent Assay. Data was statistically analysed using Graphpad Prism 8.0 at p<0.05 significance. There was significant variation in blood parasite density across treatment groups post-infection (p=0.047). A significant difference between Diminazene aceturate and IL-10 mono-treatment groups in blood parasite density (p=0.001) was observed. However, no significant variation in blood parasite density when Diminazene aceturate treatment was compared to IL-6 mono-treatment and IL- 6/IL-10 combination treatment groups (p=0.225). There was a significant difference observed in rat survival across treatment groups (p=0.0001). The results showed significant variation of CNS trypanosome Pfr2 copies across treatment groups at p<0.05. The study demonstrated that systemic administration of the anti-inflammatory cytokines IL-6 or/and IL-10 significantly reduced CNS parasitosis. Administration of IL-6 or IL-6/IL- 10 combination significantly down-regulated plasma IFN-γ and TNF-α levels (p<0.05). However, there was no significant reduction in plasma IFN-γ and TNF-α levels in IL- 10 treatment as compared to untreated infected rats. There was no significant difference in plasma IL-6 and IL-10 levels among the different treatments observed. Therefore, CNS invasion and survival of parasites may be susceptible to immunological modulation.