(91outcomes.com - May 1, 2017) -- A newly published study has found lipid changes and chronic inflammation in a first-ever published study linking data from animal models of Gulf War toxic exposures and Gulf War veterans suffering from Gulf War Illness.
The study, funded by the Congressionally-directed Gulf War Illness Research Program (GWIRP) within the Department of Defense health program, for the first time links data from Gulf War veterans participating in two different Gulf War Illness clinical research studies -- at Boston University and Nova Southeastern University near Miami -- with data from two distinct animal models of Gulf War Illness.
The animal models of Gulf War exposures were conducted at the Roskamp Institute in Sarasota, Fla. and Texas A&M University. In the GWIRP-funded studies, laboratory animals were exposed to Gulf War toxins including organophosphate pesticides and pyridostigmine bromide (contained in Gulf War nerve agent protective pills). As many as 140,000 U.S. troops to low-level sarin, another organophosphate and chemical warfare nerve agent, following demolitions of sarin-filled Iraqi munitions at an Iraqi bunker complex near Khamisiyah, Iraq in early March 1991, shortly after the Desert Storm ceasefire.
The newly published findings suggest a little before explored area of concern in Gulf War Illness -- changes in lysophospholipids, small molecules important in cellular signaling. According to a 2008 study of the biological effects of lysophospholipids, "specific lysophospholipid receptors are required for proper cardiovascular, immune, respiratory, and reproductive system development and function. Lysophospholipid receptors may also have specific roles in cancer and other diseases." (2008, Rivera & Chun).
The findings also added further evidence to a growing body of scientific studies suggesting chronic inflammation as an underlying component in Gulf War Illness.
While science is a step-by-step process, this new link between animal and human data is groundbreaking, including linking two different animal models of Gulf War Illness with the ill Gulf War veterans.
Most significantly the discovery that lysophospholipids appear to be dysregulated in both humans and animals with Gulf War toxic exposures has broad implications for biomarker and treatment development for Gulf War Illness patients.
While new treatments for Gulf War Illness based on this discovery may very well still be years away, it appears that science is edging closer to actually developing them -- progress that would not be possible without the clear Congressional treatment development guidance and continued financial support of this unique federal treatment development program.
The study results were published in the April 28, 2017 edition of PLosOne medical journal. Among the key researchers were study author Tanja Emmerich and Zuchra Zakirova, Ghania Ait-Ghezala, Laila Abdullah, James Evans, Gary Laco, Gogce Crynan, Fiona Crawford, and Michael Mullen of the Roskamp Institute in Sarasota, Fla.; Ashok Shetty, Bharathi Hattiangady and GA Shetty of the Texas A&M Health Sciences College of Medicine; Nancy Klimas of the GWIRP-funded Gulf War Illness Consortium at Nova Southeastern University near Miami; Kimberly Sullivan of the GWIRP-funded Gulf War Illness Consortium at Boston University;
SOURCE: PubMed (PLoS One), April 28, 2017, Tanja Emmerich, Fiona Crawford, et al.
PLoS One. 2017 Apr 28;12(4):e0176634. doi: 10.1371/journal.pone.0176634. eCollection 2017.
Phospholipid profiling of plasma from GW veterans and rodent models to identify potential biomarkers of Gulf War Illness.
Emmerich T1,2,3, Zakirova Z1, Klimas N4, Sullivan K5, Shetty AK6,7, Evans JE1,3, Ait-Ghezala G1,2,3, Laco GS1, Hattiangady B6,7, Shetty GA6,7, Mullan M1, Crynen G1,2, Abdullah L1,2,3, Crawford F1,2,3.
Gulf War Illness (GWI), which affects at least one fourth of the 700,000 veterans deployed to the Gulf War (GW), is characterized by persistent and heterogeneous symptoms, including pain, fatigue and cognitive problems. As a consequence, this illness remains difficult to diagnose. Rodent models have been shown to exhibit different symptomatic features of GWI following exposure to particular GW agents (e.g. pyridostigmine bromide, permethrin and DEET) and/or stress. Preclinical analyses have shown the activation of microglia and astroglia as a pathological hallmark in these mouse and rat models. Although much has been learned in recent years from these different rodent models and independent clinical studies, characterization studies to identify overlapping features of GWI in animals and humans have been missing. Thus, we aimed to identify biomarkers that co-occur in the plasma of rodent models of GWI and human GWI patients. We observed increases of multiple phospholipid (PL) species across all studied cohorts. Furthermore, these data suggested dysfunction within ether and docosahexaenoic acid and arachidonic acid containing PL species in relation to GWI. As these PL species play a role in inflammatory processes, these findings suggest a possible role for inflammatory imbalance in GWI. Overall, we show that the peripheral lipid disturbances are present both in human GWI patients and in the preclinical rodent models of GWI, highlighting the importance of lipidomics as a potential platform for further biomarker discovery and supporting the value of GW agent exposed models of GWI.