Saturday, 13 August 2016

Inflammation is part of Gulf War Syndrome

Although mostly trying to avoid any politics-talk on this blog I am going to make some reference to it in this post set in the context of the Persian Gulf War otherwise known at the First Iraq War.

The recent publication of the Chilcot report describing the case for the UK's involvement in the 2003 Iraq War (the second Iraq War) has further lit up an already illuminating year in British politics, by perhaps adding fuel to the notion that 'finishing the job' might have been an important link between the two conflicts...

Operation Desert Storm - the combat phase of the First Gulf War (1991) - described by some as 'the most toxic war in history' left a mark not just on the region where it was fought and its people but also on many of the returning service personnel, some of whom came back in a pretty poor state of health. Their various symptoms known collectively as Gulf War Syndrome or Illness, are still the topic of discussions and debate to this day despite increasing evidence that they are 'real' symptoms (see here) and not just some psychosomatic manifestation of combat stress for example, as advocated by some quite prominent figures. The possible reasons for illness are varied (see here) but when one uses the words 'sarin' in the context of potential exposures for example you get a flavour for what might have been involved [1] and their potential contributions to health or rather ill-health.

The paper by Gerhard Johnson and colleagues [2] (open-access) adds further credence to the idea that Gulf War Illness (GWI) is indeed a real phenomenon and specifically: "that inflammation is a component of the pathobiology of GWI." Based on the examination of a relatively small number of veterans (85 out of 500 deployed veterans who were invited to participate), researchers undertook a "structured interview" that "assessed their health status, and blood samples were obtained." They managed to divide veterans up into GWI+ (n=57) and GWI- (n=28) groupings dependent on whether or not they reached the Fukuda criteria [3] for a "a chronic multisymptom condition" linked to deployment to the Gulf War.

Results: over 80 specific analytes were assayed for from the blood samples provided by participants. Many compounds had an immunological slant in terms of being cytokines or being other markers of immune system (specifically inflammatory) 'activation'. "The results of the current study provide evidence of alterations in a number of blood parameters that are readily measurable in routine clinical laboratories" was the headline as six specific compounds, all with inflammation in mind, were ripe for further independent study: plasma C-reactive protein (CRP), leptin, brain-derived neurotrophic factor (BDNF), and matrix metalloproteinase-9 (MMP-9)  = higher in the GWI+ group. Heart-type fatty acid binding protein (H-FABP) and matrix metalloproteinase-2 (MMP-2) = lower in the blood of GWI+ subjects. Alongside "the distributions of peripheral blood lymphocyte, monocyte, neutrophil, and platelet counts were higher in GWI+ subjects" compared with GWI- participant data leading researchers to observe that "a model utilizing three readily measurable biomarkers [lymphocytes, monocytes, and C reactive protein]... appears to significantly augment the symptom-based case definition of GWI."

"The limitations of the study include small sample size, restricted geographic, ethnic, and sex composition of the study subjects, assay of blood parameters only once, some plasma protein assays, including cytokines, considered inevaluable due to a high percentage of assays below the level of detection, overlap of biomarker distributions within the normal range, absence of correction for multiple comparisons, a limited number of blood proteins found to be positively related to GWI+ status, and the absence of a confirmation cohort study." Apologies for just grafting a large chunk of text from the Johnson paper into this post, but when it comes to the limitations of their work, the authors do a pretty good job of cautioning against any over-hype and providing a roadmap to 'where next?'

And as part of that 'where next?' it appears that we might be talking quite soon about some findings if an associated ClinicalTrials.gov entry is anything to go by (see here) on the use of 'delayed-release prednisone' with this group. I say this without making any value judgements or providing anything that looks, sounds or smells like medical or clinical advice.

We wait and see.

And to close: "all is as the Force wills it" apparently...

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[1] Proctor SP. et al. Effects of sarin and cyclosarin exposure during the 1991 Gulf War on neurobehavioral functioning in US army veterans. Neurotoxicology. 2006 Dec;27(6):931-9.

[2] Johnson GJ. et al. Blood Biomarkers of Chronic Inflammation in Gulf War Illness. PLoS ONE 11(6): e0157855.

[3] Fukuda K. et al. Chronic multisymptom illness affecting Air Force veterans of the Gulf War. JAMA. 1998 Sep 16;280(11):981-8.

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ResearchBlogging.org Johnson GJ, Slater BC, Leis LA, Rector TS, & Bach RR (2016). Blood Biomarkers of Chronic Inflammation in Gulf War Illness. PloS one, 11 (6) PMID: 27352030