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Evidence for abnormal cytokine expression in Gulf War Illness: A preliminary analysis of daily immune monitoring data.

Parkitny L, Middleton S, Baker K, Younger J - BMC Immunol. (2015)

Bottom Line: We found that GWI was associated with higher variability in the expression of eotaxin-1 (p < 0.001).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.

View Article: PubMed Central - PubMed

Affiliation: Neuroinflammation, Pain & Fatigue Lab, University of Alabama at Birmingham, Birmingham, AL, USA. lukeparkitny@interleuk.in.

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.

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Related in: MedlinePlus

z-scored 3-day-smoothed serum IL-15 concentration (thin line) plotted against z-scored 3-day-smoothed daily self-reported fatigue (thick line), by participant. IL-15 concentration/fatigue severity are represented on the y-axis. Time is represented on the x-axis. IL-15 was selected for display as our statistical tests suggested that it was most significantly associated with fatigue severity fluctuations. Two participants did not express IL-15 at concentrations that were measurable
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Fig1: z-scored 3-day-smoothed serum IL-15 concentration (thin line) plotted against z-scored 3-day-smoothed daily self-reported fatigue (thick line), by participant. IL-15 concentration/fatigue severity are represented on the y-axis. Time is represented on the x-axis. IL-15 was selected for display as our statistical tests suggested that it was most significantly associated with fatigue severity fluctuations. Two participants did not express IL-15 at concentrations that were measurable

Mentions: In all analyses, significance was determined using a false discovery rate (FDR) corrected threshold of p = 0.0098. Results of all analyses are shown in Table 2. Because in the GWI cohort, the levels of IL-15 were most strongly correlated with day-to-day changes in fatigue severity, we have also presented time-series plots that show the relationship between IL-15 and fatigue for each individual participant (Fig. 1).Fig. 1


Evidence for abnormal cytokine expression in Gulf War Illness: A preliminary analysis of daily immune monitoring data.

Parkitny L, Middleton S, Baker K, Younger J - BMC Immunol. (2015)

z-scored 3-day-smoothed serum IL-15 concentration (thin line) plotted against z-scored 3-day-smoothed daily self-reported fatigue (thick line), by participant. IL-15 concentration/fatigue severity are represented on the y-axis. Time is represented on the x-axis. IL-15 was selected for display as our statistical tests suggested that it was most significantly associated with fatigue severity fluctuations. Two participants did not express IL-15 at concentrations that were measurable
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4589096&req=5

Fig1: z-scored 3-day-smoothed serum IL-15 concentration (thin line) plotted against z-scored 3-day-smoothed daily self-reported fatigue (thick line), by participant. IL-15 concentration/fatigue severity are represented on the y-axis. Time is represented on the x-axis. IL-15 was selected for display as our statistical tests suggested that it was most significantly associated with fatigue severity fluctuations. Two participants did not express IL-15 at concentrations that were measurable
Mentions: In all analyses, significance was determined using a false discovery rate (FDR) corrected threshold of p = 0.0098. Results of all analyses are shown in Table 2. Because in the GWI cohort, the levels of IL-15 were most strongly correlated with day-to-day changes in fatigue severity, we have also presented time-series plots that show the relationship between IL-15 and fatigue for each individual participant (Fig. 1).Fig. 1

Bottom Line: We found that GWI was associated with higher variability in the expression of eotaxin-1 (p < 0.001).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.

View Article: PubMed Central - PubMed

Affiliation: Neuroinflammation, Pain & Fatigue Lab, University of Alabama at Birmingham, Birmingham, AL, USA. lukeparkitny@interleuk.in.

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.

Show MeSH
Related in: MedlinePlus