Cytokine levels associated with experimental malaria pathology during Plasmodium berghei ANKA infection in a mouse model

Abstract

Successful recovery from malaria involves striking a balance between counteracting cytokines. The cytokine imbalance contributes to pathological features, but their exact levels have not been elucidated. This study aimed at investigating the role played by circulating cytokines in pathophysiology of cerebral malaria using experimental cerebral malaria (ECM) model by profiling four serum cytokines using cytometric bead array. 72 BALB/c mice were intraperitoneally inoculated with 0.2 ml 1×104 parasitized red blood cells at day 0 and randomized into six groups (six mice/group). The mice were sacrificed at day 4, 6, 8, 11 and 20 post-infection. Significantly higher systemic levels (P<0.05) of interferon-gamma (IFN-γ) were observed between day 8 and 20 post inoculation (p.i), while tumor necrosis factor-alpha (TNF-α) levels were significant at days 4, 8 11, 14 and 20, respectively in BALB/c mice that survived until day 20 post-infection with a higher parasitemia (up to 52.6%±0.8). Significant concentrations (P<0.05) of interleukin-4 (IL-4) were observed between day 4 and 8. IL-5 levels had significant differences at days 11 and 20 p.i. T-cell pathology was revealed by fragmentation of whole genomic DNA during the infection which coincided with elevated IFN-γ and TNF-α responses further accelerating the severity of cerebral malaria (CM). This study has demonstrated the correlation between T-lymphocyte pathology and elevated levels of T-helper 1 (Th1) cytokines concentrations in the brain and spleen.