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Abstract
Background: There is need to understand biological markers and mechanisms in Gulf War illness (GWI).
Goal: To examine whether and how eicosanoids – prostaglandins and leukotrienes – are altered in veterans with GWI.
Methods: Seventy participants including 37 GWI and 33 healthy controls, shared exposure information, and had plasma eicosanoids assessed – prostaglandin F2 alpha (pgf2α), prostaglandin D2 (pgd2), leukotriene B4 (lb4) among others. Values were compared for GWI versus controls. Eicosanoid intercorrelations were compared in cases vs. controls. For the most significantly altered eicosanoid in GWI, exposure and symptom relations were assessed.
Results: Prostaglandins and leukotrienes were depressed in GWI, strongest for pgf2α, then lb4. Eicosanoid intercorrelations differed in GWI vs. controls. Fuel-solvent, pesticide, radioactive chemicals and metal exposures related negatively to pgf2α; as, in GWI, did chemical attack and vaccines. Multivariate predictors included fuels-solvents and radioactive chemicals (negative); tetanus vaccine and herbicides (positive). Fuels-solvents and radioactive chemicals predicted lower pgf2α in cases, controls, and all participants controlled for case status. Lower pgf2α related to GWI “Kansas criteria” domains of pain, respiratory, and (borderline significantly) skin symptoms.
Conclusion: Multiple eicosanoids are depressed in GWI, particularly pgf2α and lb4. Prior fuel-solvent exposures, radioactive chemicals, and (in GWI cases) vaccines were linked to lower pgf2α.
Acknowledgements
We thank Leeann Bui for generating . Collection of demographic, military and exposure data were funded under DoD CDMRP W81XWH-10-1-0837 (Golomb, PI). Assessment of eicosanoids was funded under DoD CDMRP W81XWH-10-0663 (Repine, PI).
Additional information
Funding
Notes on contributors
Dwight Smith
John E. Repine and Dwight Smith designed the tests to be done. Beatrice Golomb designed the case-control study. Jost Klawitter, Jelena Klawitter, Uwe Christians, Paul Wilson and Nancy Elkins provided technical assistance and conceptual ideas regarding the project. Janis Ritchie with Hayley Koslik oversaw study implementation, recruitment and study visits. Beatrice Golomb drafted the manuscript. Hayley Koslik reviewed the data and analyses against entries in the manuscript, edited the manuscript and performed administrative aspects of submission.
John E. Repine
John E. Repine and Dwight Smith designed the tests to be done. Beatrice Golomb designed the case-control study. Jost Klawitter, Jelena Klawitter, Uwe Christians, Paul Wilson and Nancy Elkins provided technical assistance and conceptual ideas regarding the project. Janis Ritchie with Hayley Koslik oversaw study implementation, recruitment and study visits. Beatrice Golomb drafted the manuscript. Hayley Koslik reviewed the data and analyses against entries in the manuscript, edited the manuscript and performed administrative aspects of submission.