IL-17 and IL-17C Signaling Protects the Intestinal Epithelium against Diisopropyl Fluorophosphate Exposure in an Acute Model of Gulf War Veterans' Illnesses

Chemical exposures and suspected impact on Gulf War Veterans

“…They concluded that DFP-exposed mice significantly reduced tight junction proteins (claudin-4 and occludin) and their corresponding mRNA expression in the large intestine. This study also found that the loss of IL-17, a pro-inflammatory cytokine with protective properties in the intestinal epithelium, can exacerbate tight junction reduction in an acute model of GWI [17]. Moreover, exposure to DFP has led to a significant decrease in the antimicrobial peptide (AMP) secreted by intestinal epithelial cells.…”

“…Moreover, exposure to DFP has led to a significant decrease in the antimicrobial peptide (AMP) secreted by intestinal epithelial cells. The loss of AMP compromises the intestinal microbiome and may underlie to dysbiosis [17]. Collectively, these works implicate that gut decontamination of GWI patients coupled with restoring a healthy gut microbiome and introducing essential bacterial metabolites such as butyrate and intestinal cytokines such as IL-17 may attenuate certain symptoms with the caveat that additional research is a requirement before clinical testing can be justified.…”

“…Other recent work also suggests that gut dysbiosis as a result of GW chemical exposure can be an initiator of the pro-inflammatory effects of GWI [28]. Exposing a rodent to CORT followed by PB and Permethrin [28] or DFP [17] results in significant alteration of intestinal microbiome composition. Moreover, transformation of the microbiome composition is associated with the reduction of healthy gut bacteria, while the loss of healthy gut bacteria will drastically impact the expression of the tight junction proteins occludin (decreased) and claudin-2 (increased) [29].…”

“…Another study, led by Patterson et al [17], investigated the effects of DFP exposure on intestinal epithelium. They concluded that DFP-exposed mice significantly reduced tight junction proteins (claudin-4 and occludin) and their corresponding mRNA expression in the large intestine.…”