The online version of this article (doi:10.1186/s12936-017-2001-y) contains supplementary material, which is available to authorized users.
Izabella Surowiec and Sandra Gouveia-Figueira contributed equally to this work
Johan Normark and Johan Trygg contributed equally to this work
Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism.
Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA®) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis).
Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls.
It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed.
Additional file 1. Clinical information for the control patients included in the study.
Additional file 2. Clinical information for the uncomplicated malaria patients included in the study.
Additional file 3. Clinical information for the severe malaria patients included in the study.
Additional file 4. Patient selection procedure.
Additional file 5. Native standards and corresponding internal standards used in the study.
Additional file 6. Standard concentrations used for calibration curves of endocannabinoids and related lipids.
Additional file 7. Standard concentrations (pg/mL) used for calibration curves of oxylipins.
Additional file 8. Parameters of models for oxylipins discussed in the study.
Additional file 9. Parameters of models for endocannabinoids discussed in the study.
Additional file 10. Oxylipin levels (pM) in the blood serum samples form controls, uncomplicated malaria and severe malaria patients.
Additional file 11. OPLS-DA correlation loadings from the uncomplicated versus controls and severe versus controls models.
Additional file 12. Scatter plots for oxylipins that showed significant p-values in between group comparisons.
Additional file 13. Correlation of oxylipin levels with temperature.
Additional file 14. ROC curves results for oxylipins.
Additional file 15. Endocannabinoids levels (pM) in the blood serum samples from controls, uncomplicated malaria and severe malaria patients.
Additional file 16. OPLS-DA correlation loadings from the uncomplicated versus controls and severe versus controls models.
Additional file 17. Scatter plots for endocannabinoids that showed significant p-values in between group comparisons.
Additional file 18. Correlation of OEA and EPEA with parasitaemia values.
Additional file 19. ROC curves results for endocannabinoids.
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