Fibrogenic cytokine levels in bronchoalveolar lavage aspirates 15 years after exposure to sulfur mustard

Abstract

Over 100,000 Iranian war veterans suffer from chronic effects of mustard gas exposure. Sulfur mustard was used by Iraq during the Iraqi-imposed war on Iran (between 1980 and 1988). The major complaints of these patients are mild interstitial fibrosis and bronchiolitis. We aimed to determine the state of fibrosis progression and assessed transforming growth factor (TGF)-beta1 levels in pulmonary samples and in bronchoalveolar lavage (BAL) aspirates. A total of 126 war veterans confirmed for lung disease were assessed and compared with three control groups: 1) 64 veterans not exposed to chemical agents, 2) 12 idiopathic pulmonary fibrosis civilian patients, and 3) 33 normal persons. BAL was performed via a flexible fiber-optic bronchoscope and the standard manual method. Total protein was measured by Bradford assay, and samples were corrected with regard to coefficients. Samples were concentrated 15-fold by lyophilization and resolubilization. Samples were double-checked using an ELISA test kit. The Mann-Whitney test was used for the data analysis using commercial software. We detected that significant differences between TGF-beta1 levels between the case group and control group 1 (P = 0.001) and control group 3 (P = 0.003). No significant differences were found between the case group and control group 2 (P = 0.57). Inflammation and fibrotic processes in lung tissue of patients exposed to sulfur mustard may be progressive so IFN-gamma may be a useful drug to these patients' treatment.

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

“…The catalytic antioxidant treatment significantly attenuated SM-mediated increases in TNF-a, IL-6, KC/GRO, and IL-1b at 24 h. Transforming growth factor b1 (TGFb1) is commonly associated with lung injury and repair responses (Liu, 2008;Tatler and Jenkins, 2012). TGFb1 has been implicated in the development of pulmonary fibrosis in chronic models of SM exposure (Aghanouri et al, 2004;Emad and Emad, 2007;Ghanei and Harandi, 2011;Poursaleh et al, 2012). SM exposure significantly increased BALF TGFb1 levels nearly 10-fold over Sham PBS at 24 h post-exposure (Fig.…”

“…It was discovered that this growth factor is elevated in the acute model of SM toxicity, and that antioxidant dosing acutely inhibits this overexpression. TGFb1 levels are heavily associated with the development of idiopathic pulmonary fibrosis, and it has previously been described that levels of TGFb1 can be upregulated long after exposure to SM (Aghanouri et al, 2004;Tatler and Jenkins, 2012). The antioxidant induced suppression of TGFb1 levels could indicate that antioxidants may be beneficial for chronic pulmonary conditions following SM inhalation as well as resolving acute toxicity.…”

Sulfur mustard and respiratory diseases: Revisit with special reference to the “Comments on ‘Sulfur Mustard and Respiratory Diseases’, Tang and Loke () and a prepared Integrated Mechanism for Chronic Pulmonary Disease from Exposure to Sulfur Mustard” by Saburi and Ghanei ()

“…As it could be seen from Table 1, cytokines and chemokines have been well investigated in victims exposed to mustard by Emad, Ghanei and their colleagues from two different research groups in Iran (Aghanouri et al, 2004;Amiri et al, 2009;Attaran et al, 2010;Emad & Emad, 2007a,b,c,d,e;Ghazanfari et al, 2009;Pourfarzam et al, 2009;Yaraee et al, 2009;Zarin et al, 2010). 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.…”

“…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).…”

Rikkunshito ameliorates bleomycin-induced acute lung injury in a ghrelin-independent manner

“…Cell differentials were determined by counting 300 cells under ϫ400 magnification. The amount of total protein in the BALF supernatant was measured by the Bradford assay (1).…”