Gulf War Illness-associated increases in blood levels of interleukin 6 and C-reactive protein: biomarker evidence of inflammation

Butterick, Tammy A.; Trembley, Janeen H.; Stone, Laura L. Hocum; Muller, Clemma; Rudquist, Rebecca R.; Bach, Ronald R.

doi:10.1186/s13104-019-4855-2

Cited by 35 publications

(41 citation statements)

References 19 publications

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“…Neuroimaging has been found to be useful as a differential diagnostic tool for GW ill versus GW healthy individuals; however, what has been missing is the ability to use a less invasive, more readily available, and less costly tool, such as blood biomarkers to differentiate GWI from GW healthy status and differentiate GWI from another chronic multisymptom discord [ 6 , 8 ]. There have been some encouraging blood biomarker studies reporting differences between GWI cases and controls on neuroinflammatory markers that require validation in other GWI cohorts [ 9 , 10 , 11 ]. In addition, recently, we reported on a pilot study of serum biomarkers, which found seven out of eight markers significantly differed in veterans with GWI versus symptomatic controls with lower back pain, suggesting new potential blood markers for GWI [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls

et al. 2020

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For the past 30 years, there has been a lack of objective tools for diagnosing Gulf War Illness (GWI), which is largely characterized by central nervous system (CNS) symptoms emerging from 1991 Gulf War (GW) veterans. In a recent preliminary study, we reported the presence of autoantibodies against CNS proteins in the blood of veterans with GWI, suggesting a potential objective biomarker for the disorder. Now, we report the results of a larger, confirmatory study of these objective biomarkers in 171 veterans with GWI compared to 60 healthy GW veteran controls and 85 symptomatic civilian controls (n = 50 myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and n = 35 irritable bowel syndrome (IBS)). Specifically, we compared plasma markers of CNS autoantibodies for diagnostic characteristics of the four groups (GWI, GW controls, ME/CFS, IBS). For veterans with GWI, the results showed statistically increased levels of nine of the ten autoantibodies against neuronal “tubulin, neurofilament protein (NFP), Microtubule Associated Protein-2 (MAP-2), Microtubule Associated Protein-Tau (Tau), alpha synuclein (α-syn), calcium calmodulin kinase II (CaMKII)” and glial proteins “Glial Fibrillary Acidic Protein (GFAP), Myelin Associated Glycoprotein (MAG), Myelin Basic Protein (MBP), S100B” compared to healthy GW controls as well as civilians with ME/CFS and IBS. Next, we summed all of the means of the CNS autoantibodies for each group into a new index score called the Neurodegeneration Index (NDI). The NDI was calculated for each tested group and showed veterans with GWI had statistically significantly higher NDI values than all three control groups. The present study confirmed the utility of the use of plasma autoantibodies for CNS proteins to distinguish among veterans with GWI and other healthy and symptomatic control groups.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls

et al. 2020

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“…GWI animal models have validated the involvement of neuroinflammatory mechanisms in the pathology of the disease ( 10 ), including the over-reactivity of astrocytes and microglia. This increased activation of immune cells was also directly observed in the brain of veterans with GWI ( 11 ), while inflammatory biomarkers such as elevated levels of pro-inflammatory cytokines, IL-1β, INF-γ, or IL-6 ( 12 , 13 ) have been found in the serum of GWI patients. Increased concentrations of inflammatory cytokines are also associated with different mood disorders, including bipolar and major depressive disorders ( 14 , 15 ).…”

Section: Introductionmentioning

confidence: 74%

“…inflammatory biomarkers such as elevated levels of proinflammatory cytokines, IL-1b, INF-g, or IL-6 (12,13) have been found in the serum of GWI patients. Increased concentrations of inflammatory cytokines are also associated with different mood disorders, including bipolar and major depressive disorders (14,15).…”

Section: Introductionmentioning

confidence: 99%

The Innate Immune System and Inflammatory Priming: Potential Mechanistic Factors in Mood Disorders and Gulf War Illness

et al. 2020

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Gulf War Illness is a chronic multisystem disorder affecting approximately a third of the Veterans of the Gulf War, manifesting with physical and mental health symptoms such as cognitive impairment, neurological abnormalities, and dysregulation of mood. Among the leading theories into the etiology of this multisystem disorder is environmental exposure to the various neurotoxins encountered in the Gulf Theatre, including organophosphates, nerve agents, pyridostigmine bromide, smoke from oil well fires, and depleted uranium. The relationship of toxin exposure and the pathogenesis of Gulf War Illness converges on the innate immune system: a nonspecific form of immunity ubiquitous in nature that acts to respond to both exogenous and endogenous insults. Activation of the innate immune system results in inflammation mediated by the release of cytokines. Cytokine mediated neuroinflammation has been demonstrated in a number of psychiatric conditions and may help explain the larger than expected population of Gulf War Veterans afflicted with a mood disorder. Several of the environmental toxins encountered by soldiers during the first Gulf War have been shown to cause upregulation of inflammatory mediators after chronic exposure, even at low levels. This act of inflammatory priming, by which repeated exposure to chronic subthreshold insults elicits robust responses, even after an extended period of latency, is integral in the connection of Gulf War Illness and comorbid mood disorders. Further developing the understanding of the relationship between environmental toxin exposure, innate immune activation, and pathogenesis of disease in the Gulf War Veterans population, may yield novel therapeutic targets, and a greater understanding of disease pathology and subsequently prevention.

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“…As previous reports, excessive neuroin ammation presented in veterans suffering from GWI and also observed in animal model of GWI 21,41 . Part of serum proteins associated with in ammation were signi cantly increased in veterans suffering from GWI, including interleukin 6, C-reactive protein, matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) 42,43 . In animal model of GWI, suppression of the in ammatory responses showed a neuroprotective effect, improved neurogenesis, and better cognitive and mood function 44 .…”

Section: Discussionmentioning

confidence: 99%

Minocycline Alleviate A Rat Model Of Gulf War Illness Via Altering Gut Microbiome, Attenuating Neuroinflammation And Enhancing Hippocampal Neurogenesis

Liu¹,

Wang²,

Du³

et al. 2020

Preprint

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Background: Accumulating evidence suggests that deficits in neurogenesis, chronic inflammation and gut microbiome dysregulation contribute to the pathophysiology of Gulf War Illness (GWI). Minocycline has been demonstrated to be a potent neuroprotective agent and could regulate neuroinflammation. The present study intended to investigate whether treatment of minocycline maintain better cognition and mood function in a rat model of GWI and the potential mechanism. Methods: Rats received 28 days of GWI-related chemical exposure and restraint stress, along with daily minocycline or vehicle treatment. Cognitive and mood function, neuroinflammation, neurogenesis and gut microbiota were detected.Results: We found that minocycline treatment induced better cognitive and mood function in a GWI rat model, as indicated by open-field test, elevated plus maze test, novel object recognition test and forced swim test. Moreover, minocycline treatment reversed the altered gut microbiome, neuroinflammation and the decreased hippocampal neurogenesis of rats with GWI. Conclusion: Taken together, our study indicated that minocycline treatment exerts better cognitive and mood function in GWI rat model, which is possible related to gut microbiota remodeling, restrained inflammation and enhanced hippocampal neurogenesis. These results may establish minocycline a potential prophylactic or therapeutic agent for the treatment of GWI.

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Gulf War Illness-associated increases in blood levels of interleukin 6 and C-reactive protein: biomarker evidence of inflammation

Cited by 35 publications

References 19 publications

RETRACTED: Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls

RETRACTED: Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls

The Innate Immune System and Inflammatory Priming: Potential Mechanistic Factors in Mood Disorders and Gulf War Illness

Minocycline Alleviate A Rat Model Of Gulf War Illness Via Altering Gut Microbiome, Attenuating Neuroinflammation And Enhancing Hippocampal Neurogenesis

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