Corticosteroid treatment inhibits airway hyperresponsiveness and lung injury in a murine model of chemical-induced airway inflammation

Wigenstam, Elisabeth; Jonasson, Sofia; Koch, Bo; Bucht, Anders

doi:10.1016/j.tox.2012.06.020

Cited by 25 publications

(24 citation statements)

References 41 publications

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“…Accumulating evidence from both experimental and human exposures suggests an involvement of inflammatory cells and mediators they release in vesicant-induced lung injury (Weinberger et al, 2011; Wigenstam et al, 2012). Of particular interest is tumor necrosis factor (TNF)α, a macrophage-derived pro-inflammatory cytokine rapidly generated in the lung in response to injury induced by vesicants (Malaviya et al, 2010; Sunil et al, 2011b; Sunil et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation

Sunil

Vayas

Cervelli

et al. 2014

Experimental and Molecular Pathology

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Nitrogen mustard (NM) is a toxic alkylating agent that causes damage to the respiratory tract. Evidence suggests that macrophages and inflammatory mediators including tumor necrosis factor (TNF)α contribute to pulmonary injury. Pentoxifylline is a TNFα inhibitor known to suppress inflammation. In these studies, we analyzed the ability of pentoxifylline to mitigate NM-induced lung injury and inflammation. Exposure of male Wistar rats (250 g; 8–10 weeks) to NM (0.125 mg/kg, i.t.) resulted in severe histolopathological changes in the lung within 3 d of exposure, along with increases in bronchoalveolar lavage (BAL) cell number and protein, indicating inflammation and alveolar-epithelial barrier dysfunction. This was associated with increases in oxidative stress proteins including lipocalin (Lcn)2 and heme oxygenase (HO)-1 in the lung, along with pro-inflammatory/cytotoxic (COX-2+ and MMP-9+), and anti-inflammatory/wound repair (CD163+ and Gal-3+) macrophages. Treatment of rats with pentoxifylline (46.7 mg/kg, i.p.) daily for 3 d beginning 15 min after NM significantly reduced NM-induced lung injury, inflammation, and oxidative stress, as measured histologically and by decreases in BAL cell and protein content, and levels of HO-1 and Lcn2. Macrophages expressing COX-2 and MMP-9 also decreased after pentoxifylline, while CD163+ and Gal-3+ macrophages increased. This was correlated with persistent upregulation of markers of wound repair including pro-surfactant protein-C and proliferating nuclear cell antigen by Type II cells. NM-induced lung injury and inflammation were associated with alterations in the elastic properties of the lung, however these were largely unaltered by pentoxifylline. These data suggest that pentoxifylline may be useful in treating acute lung injury, inflammation and oxidative stress induced by vesicants.

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Section: Introductionmentioning

confidence: 99%

Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation

Sunil

Vayas

Cervelli

et al. 2014

Experimental and Molecular Pathology

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“…Neutrophils in other organs i.e. the lung are important part of the early innate immune response, as early as 4 hr post exposure to different antigen challenges [26,27], and can be involved in long term inflammation [28]. After the initial infiltration of the neutrophils into the tissue, the resident macrophages (Kupffer cells) may take over the immune response to the nanomaterials.…”

Section: Resultsmentioning

confidence: 99%

Engineered Nanomaterial Impact in the Liver following Exposure via an Intravenous Route–The Role of Polymorphonuclear Leukocytes and Gene Expression in the Organ

Kermanizadeh¹,

Brown²,

Hutchison

et al. 2012

J Nanomedic Nanotechnol

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“…In animal models melphalan exposure leads to a burst of proinflammatory interleukins, subsequent lung infiltration by neutrophils within 24 hours, and then a sustained lymphocytic response over days to weeks resulting in lung fibrosis [31]. Early treatment with steroids reduced alkylator-induced airway inflammation and collagen deposition in a mouse model [32]. Our review did not reveal a pattern of factors that would suggest specific risk for chlorambucil-induced interstitial pneumonitis, other than male predominance.…”

Section: Discussionmentioning

confidence: 95%

Chlorambucil-Induced Acute Interstitial Pneumonitis

Shafqat

Olszewski

2014

Case Reports in Hematology

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Chlorambucil is an alkylating agent commonly used in treatment of chronic lymphocytic leukemia (CLL). We report a case of interstitial pneumonitis developing in an 83-year-old man 1.5 months after completing a six-month course of chlorambucil for CLL. The interstitial pneumonitis responded to therapy with prednisone. We performed a systematic review of literature and identified 13 other case reports of chlorambucil-induced pulmonary toxicity, particularly interstitial pneumonitis. No unifying risk factor could be discerned and the mechanism of injury remains unknown. In contrast, major randomized trials of chlorambucil therapy in CLL have not reported interstitial pneumonitis as an adverse effect, which may be due to the rarity of the phenomenon or due to underreporting of events occurring after completion of treatment. Clinicians should consider drug-induced interstitial pneumonitis in the differential diagnosis of a suggestive syndrome developing even after discontinuation of chlorambucil.

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Corticosteroid treatment inhibits airway hyperresponsiveness and lung injury in a murine model of chemical-induced airway inflammation

Cited by 25 publications

References 41 publications

Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation

Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation

Engineered Nanomaterial Impact in the Liver following Exposure via an Intravenous Route–The Role of Polymorphonuclear Leukocytes and Gene Expression in the Organ

Chlorambucil-Induced Acute Interstitial Pneumonitis

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