Inflammatory cytokine response in sulfur mustard-exposed mouse skin†‡

Ricketts, Karen M.; Santai, C. T.; Graziosi, Agnese; Doyel, T. D.; Gazaway, Michelle Y.; Casillas, Robert P.

doi:10.1002/1099-1263(200012)20:1+<::aid-jat685>3.0.co;2-h

Cited by 60 publications

(65 citation statements)

References 19 publications

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“…For each marker tested, treatment with AEOL 10150 was able to restore BALF cytokine concentrations back to control values. Published research linking inflammatory responses to injury progression after exposure to SM analogs support the idea that an indirect reduction in inflammation from antioxidant treatment may reinforce the protective effect it displays against SM toxicity (Arroyo et al, 1995;Emmler et al, 2007;Kehe et al, 2009;O'Neill et al, 2010;Ricketts et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…were selected to determine if antioxidant treatments would affect their presence in bronchoalveolar lavage fluid (BALF) (Emmler et al, 2007;Malaviya et al, 2010;Ricketts et al, 2000;Seagrave et al, 2010;Zhu et al, 2014). The cytokines were analyzed using a proinflammatory multiplex panel that included cytokines previously reported to be elevated by SM exposure.…”

Section: Discussionmentioning

confidence: 99%

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From the Cover: Catalytic Antioxidant Rescue of Inhaled Sulfur Mustard Toxicity

et al. 2016

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Sulfur mustard (bis 2-chloroethyl ethyl sulfide, SM) is a powerful bi-functional vesicating chemical warfare agent. SM tissue injury is partially mediated by the overproduction of reactive oxygen species resulting in oxidative stress. We hypothesized that using a catalytic antioxidant (AEOL 10150) to alleviate oxidative stress and secondary inflammation following exposure to SM would attenuate the toxic effects of SM inhalation. Adult male rats were intubated and exposed to SM (1.4 mg/kg), a dose that produces an LD 50 at approximately 24 h. Rats were randomized and treated via subcutaneous injection with either sterile PBS or AEOL 10150 (5 mg/kg, sc, every 4 h) beginning 1 h post-SM exposure. Rats were euthanized between 6 and 48 h after exposure to SM and survival and markers of injury were determined. Catalytic antioxidant treatment improved survival after SM inhalation in a dose-dependent manner, up to 52% over SM PBS at 48 h post-exposure. This improvement was sustained for at least 72 h after SM exposure when treatments were stopped after 48 h. Non-invasive monitoring throughout the duration of the studies also revealed blood oxygen saturations were improved by 10% and clinical scores were reduced by 57% after SM exposure in the catalytic antioxidant treatment group. Tissue analysis showed catalytic antioxidant therapy was able to decrease airway cast formation by 69% at 48 h post-exposure. To investigate antioxidant induced changes at the peak of injury, several biomarkers of oxidative stress and inflammation were evaluated at 24 h post-exposure. AEOL 10150 attenuated SM-mediated lung lipid oxidation, nitrosative stress and many proinflammatory cytokines. The findings indicate that catalytic antioxidants may be useful medical countermeasure against inhaled SM exposure.Key words: sulfur mustard; chemical weapons; antioxidant.Sulfur mustard (SM) is a chemical warfare agent possessing strong alkylating properties that induces inflammation and tissue necrosis. SM exposure produces delayed and highly incapacitating injuries that can be lethal (Anderson, 2015). SM was used during World War I and is still maintained in the chemical weapons arsenals of several countries (Kehe and Szinicz, 2005). A specific and effective antidote is not available for use after SM exposure despite research conducted for nearly 100 years (Kehe and Szinicz, 2005). The population most at risk for exposure to SM is comprised of soldiers and individuals working or living near storage depots, but SM is also considered to be a potential terrorist threat due to its low cost of production and simple synthesis.Sulfur mustard (SM) vapor adversely affects the skin, eyes, and the respiratory tract. The respiratory tract is highly

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

From the Cover: Catalytic Antioxidant Rescue of Inhaled Sulfur Mustard Toxicity

et al. 2016

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“…The studies on short term effects showed that both cellular and humoral immune functions are impaired [8]. Some experimental models showed that shortly after SM exposure, cytokine production increases strongly [29] [30].…”

Section: H Sheibani Et Almentioning

confidence: 99%

Measuring Tumor Necrosis Factor-Alpha and Interleukin-1 Beta Levels in Mustard Gas Exposed Patients

Sheibani¹,

Goudarzi²,

Esfandiari³

et al. 2017

ABB

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Sulfur mustard (SM) is an alkalizing chemical which has been used mostly as a weapon all over the world. Sulfur mustard can cause damages to many organs, especially the skin, respiratory system and the eyes. Generally, many complications of mustard gas result from its alkalizing potency and reaction with cellular components like DNA, RNA, proteins and lipid membranes. The damages caused by SM will lead to many complications which persist during the lifespan of exposed subjects. Pro-inflammatory cytokines including especially TNF-α and IL-1β can cause systemic inflammatory reactions and vast changes like altered cell signaling, migration, cytokine production changes and fever. This study was designed to analyze cytokine levels in mustardgas-exposed people's serum in the war between Iraq and Iran, who had the chronic dry-eye symptoms compared to the normal group, 30 years after exposure. In this study, 25 veterans who were exposed to mustard gas were compared to 25 healthy people as control group. The veterans with concurrent involvement of eye, lung, and skin were selected. We used ELISA method to assess the levels of TNF-α and IL-1β in serum of people in both groups. All the results analyzed with T-test in SPSS 17 statistical software. The mean levels of TNF-α and IL-1β in serum of chemical exposed veterans were 52.3 ± 1.4 pg/ml and 3.43 ± 0.3 pg/ml while in the control group were 19.5±1.3 pg/ml and 2.25 ± 0.2 pg/ml, respectively. In the control group, the serum pro-inflammatory cytokine levels were significantly lower than the exposed group (P < 0.05). This study showed that there is a meaningful difference be-

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“…However, results from Emad's group, and some of Ghanei's group (such as Aghanouri et al, 2004;Attaran et al 2010;Zarin et al, 2010) are more relevant to pulmonary diseases as they focused on localized tissue changes of cytokines and chemokines in bronchoalveolar lavage fluid or lung biopsies. To link changes of cytokines and chemokines at system level (in serum) to pulmonary diseases may be too speculative as it has been well known that mustard could also induce inflammatory (cytokine and chemokine) changes in other organs such as skin (Arroyo et al, 2000(Arroyo et al, , 2003(Arroyo et al, , 2004Blaha et al, 2000a,b;Cowan et al, 2002;Kehe et al, 2009;Ricketts et al, 2000;Sabourin et al, 2002;Tanaka et al, 1997;Tsuruta et al, 1996;Wormser et al, 2005), eye (Ghasemi et al, 2012), liver (Anand et al, 2009). …”

Section: Cytokines and Pulmonary Disordersmentioning

confidence: 99%