title: Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis.
abstract: Gulf War illness (GWI) is a chronic disease of unknown etiology characterized by persistent symptoms such as cognitive impairment, unexplained fatigue, pervasive pain, headaches, and gastrointestinal abnormalities. Current reports suggest that as many as 200,000 veterans who served in the 1990-1991 Persian Gulf War were afflicted. Several potential triggers of GWI have been proposed including chemical exposure, toxins, vaccines, and unknown infectious agents. However, a definitive cause of GWI has not been identified and a specific biological marker that can consistently delineate the disease has not been defined. Myalgic encephalomyelitis (ME) is a disease with similar and overlapping symptomology, and subjects diagnosed with GWI typically fit the diagnostic criteria for ME. For these reasons, GWI is often considered a subgroup of ME. To explore this possibility and identify immune parameters that may help to understand GWI pathophysiology, we measured 77 serum cytokines in subjects with GWI and compared these data to that of subjects with ME as well as healthy controls. Our analysis identified a group of cytokines that identified ME and GWI cases with sensitivities of 92.5% and 64.9%, respectively. The five most significant cytokines in decreasing order of importance were IL-7, IL-4, TNF-α, IL-13, and IL-17F. When delineating GWI and ME cases from healthy controls, the observed specificity was only 33.3%, suggesting that with respect to cytokine expression, GWI cases resemble control subjects to a greater extent than ME cases across a number of parameters. These results imply that serum cytokines are representative of ME pathology to a greater extent than GWI and further suggest that the two diseases have distinct immune profiles despite their overlapping symptomology.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nevada School of Medicine, Reno, NV, USA; WPI, Reno, NV, USA.
authors.forename: Svetlana F
authors.initials: SF
authors.lastname: Khaiboullina
authors.affiliation: WPI, Reno, NV, USA.
authors.forename: Kenny L
authors.initials: KL
authors.lastname: DeMeirleir
authors.affiliation: WPI, Reno, NV, USA.
authors.forename: Shanti
authors.initials: S
authors.lastname: Rawat
authors.affiliation: WPI, Reno, NV, USA.
authors.forename: Grady S
authors.initials: GS
authors.lastname: Berk
authors.affiliation: Sierra Veterans Research and Education Foundation, VA Sierra Nevada Health Care System, Reno, NV, USA.
authors.forename: Rory S
authors.initials: RS
authors.lastname: Gaynor-Berk
authors.affiliation: R.E.D Laboratories, Zellik, Belgium.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Mijatovic
authors.affiliation: WPI, Reno, NV, USA; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Republic of Tatarstan, Russian Federation.
authors.forename: Natalia
authors.initials: N
authors.lastname: Blatt
authors.affiliation: WPI, Reno, NV, USA; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Republic of Tatarstan, Russian Federation.
authors.forename: Albert A
authors.initials: AA
authors.lastname: Rizvanov
authors.affiliation: Sierra Veterans Research and Education Foundation, VA Sierra Nevada Health Care System, Reno, NV, USA.
authors.forename: Sheila G
authors.initials: SG
authors.lastname: Young
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nevada School of Medicine, Reno, NV, USA; WPI, Reno, NV, USA; Sierra Veterans Research and Education Foundation, VA Sierra Nevada Health Care System, Reno, NV, USA. Electronic address: vlombardi@medicine.nevada.edu.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Lombardi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D015415:Biomarkers / Q000097:blood*; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D015673:Fatigue Syndrome, Chronic / Q000276:immunology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015851:Interleukin-7 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018923:Persian Gulf Syndrome / Q000276:immunology* / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018793:Interleukin-13; D020381:Interleukin-17; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4
keywords: Cytokines; Gulf War illness; Myalgic encephalomyelitis; Random forest: interleukin-7