title: Evidence for abnormal cytokine expression in Gulf War Illness: A preliminary analysis of daily immune monitoring data.
abstract: BACKGROUND
  Gulf War Illness (GWI) is a clinically heterogeneous chronic condition that affects many veterans of the 1990-1991 Persian Gulf War. One of the most prevalent and debilitating symptoms of GWI is abnormal fatigue. The mechanisms underlying GWI generally, and fatigue symptoms specifically, have yet to be conclusively identified, although immune system abnormalities are suspected to be involved. The first goal of this immune monitoring study was to determine if GWI is associated with higher absolute levels and daily variability of pro-inflammatory immune factors. The second goal was to explore the relationship between day-to-day immune marker fluctuations and daily self-reported fatigue severity.
  
  
  METHODS
  We recruited veterans with GWI and healthy veteran control (HV) participants to provide self-reported fatigue severity data and blood samples, over 25 consecutive days. We profiled inflammatory processes by using a longitudinal, daily immune-monitoring approach. For each day, serum cytokine and chemokine concentrations were determined using multiplex assays.
  
  
  RESULTS
  Seven veterans with GWI and eight healthy veteran control (HV) participants completed the study protocol. We found that GWI was associated with higher variability in the expression of eotaxin-1 (p < 0.001). For GWI participants, higher fatigue severity days were associated with greater IL-1β (p = 0.008) and IL-15 (p < 0.001).
  
  
  CONCLUSIONS
  Our findings provide preliminary evidence that the immune system is involved in the pathophysiology of GWI. Longitudinal immune profiling approaches may be helpful in discovering targets for novel therapies in conditions such as GWI.
authors.affiliation: Neuroinflammation, Pain & Fatigue Lab, University of Alabama at Birmingham, Birmingham, AL, USA. lukeparkitny@interleuk.in.
authors.forename: Luke
authors.initials: L
authors.lastname: Parkitny
authors.affiliation: Department of Anesthesia, Perioperative, and Pain Medicine, Stanford University, Palo Alto, CA, USA. skmiddle@stanford.edu.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Middleton
authors.affiliation: Experimental Neuropsychology Research Unit, School of Psychological Sciences, Monash University, Melbourne, Australia. Katharine.baker@monash.edu.
authors.forename: Katharine
authors.initials: K
authors.lastname: Baker
authors.affiliation: Neuroinflammation, Pain & Fatigue Lab, University of Alabama at Birmingham, Birmingham, AL, USA. younger@uab.edu.
authors.forename: Jarred
authors.initials: J
authors.lastname: Younger
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D003710:Demography; D006801:Humans; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D018923:Persian Gulf Syndrome / Q000097:blood* / Q000276:immunology*; D013223:Statistics as Topic; D014728:Veterans
chemical_list: D016207:Cytokines