Macrophage migration inhibitory factor is associated with mortality in cerebral malaria patients in India

Vidhan Jain,Shannon Mcclintock,Venkatachalam Udhayakumar,Naomi W Lucchi,Aditya P Dash,Avinash C Nagpal,Jonathan K Stiles,Neeru Singh

doi:10.1186/1756-0500-2-36

Abstract

BackgroundMacrophage migration inhibitory factor (MIF) is a multifunctional cytokine implicated in the pathogenesis of a number of human diseases including inflammatory neurological diseases. Its role in the pathogenesis of cerebral malaria is unknown. Cerebral malaria is a life-threatening complication of falciparum malaria with approximately 20%–30% of patients dying despite appropriate anti-malarial treatment. The reason for this cerebral malaria mortality is still unknown although host proinflammatory factors have been shown to be evidently important. The current study investigated the role of circulating MIF in the pathogenesis and outcomes of cerebral malaria.FindingsThree categories of subjects contributed to this study: healthy controls subjects, mild malaria patients, and cerebral malaria patients. The cerebral malaria patients were further grouped into cerebral malaria survivors and cerebral malaria non-survivors. MIF levels in the peripheral blood plasma, obtained at the time of enrollment, were measured using standard ELISA methods. In logistic regression on cerebral malaria patients, log MIF levels were found to be significantly associated with fatal outcome (odds ratio 4.0; 95%CI 1.6, 9.8; p = 0.003). In multinomial logistic regression log MIF levels were found to be significantly associated with patient category (p = 0.004).ConclusionThis study suggests that elevated levels of MIF in the peripheral blood of cerebral malaria patients may be associated with fatal outcomes.

Highlights

Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine implicated in the pathogenesis of a number of human diseases including inflammatory neurological diseases
Multinomial logistic regression was used for all patients to determine if there was an association with patient category (HC, mild malaria (MM), CM survivors (CMS), and CM non-survivors (CMNS)) and log MIF levels, using healthy controls (HC) as the reference group
The highest median MIF level was in the CMNS group, followed by HC, MM, and CMS, respectively (Figure 1)

Summary

Introduction

Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine implicated in the pathogenesis of a number of human diseases including inflammatory neurological diseases. Cerebral malaria is a lifethreatening complication of falciparum malaria with approximately 20%–30% of patients dying despite appropriate anti-malarial treatment. The reason for this cerebral malaria mortality is still unknown host proinflammatory factors have been shown to be important. A recent study demonstrated a decline in MIF levels during an experimental malaria infection using healthy European volunteers [4]. These studies have suggested a protective role for MIF during malaria. Pregnant women with placental malaria infection demonstrated significantly higher levels of MIF in the placental intervillous blood compared to uninfected pregnant women [5,6]

Methods

Results

Conclusion