What question did this study set out to answer?

Determine whether locally produced tumor necrosis factor-alpha mediates acute microvascular lung injury and inflammation following interleukin-2 administration in a rat model.

February 1, 1996Circulation Research

Locally Produced Tumor Necrosis Factor-α Mediates Interleukin-2Induced Lung Injury

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Authors

RRReuven RabinoviciBoston University GFG FeuersteinLa Roche College FAF. AbdullahUniversity of Toronto

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Implication

Preclinical study demonstrates that local TNF-alpha mediates interleukin-2-induced lung injury in rats, highlighting potential therapies to reduce immunotherapy toxicity.

Key Points

Determine whether locally produced tumor necrosis factor-alpha mediates acute microvascular lung injury and inflammation following interleukin-2 administration in a rat model.
Administered recombinant human interleukin-2 (10^6 U IV, n=6) to rats to induce experimental pulmonary toxicity.
Pretreated cohorts with an anti-tumor necrosis factor-alpha monoclonal antibody (25 mg/kg IV, n=7) or the synthesis inhibitor rolipram (200 µg/kg IV, n=7).
Measured lung water, myeloperoxidase activity, bronchoalveolar lavage protein accumulation, tissue hypoxia, and localized cytokine and adhesion molecule mRNA expression.
Interleukin-2 elevated lung water, myeloperoxidase activity, protein accumulation, and lung tissue tumor necrosis factor-alpha levels (1543 ± 496 pg/g lung wet weight) localized to alveolar macrophages, while serum tumor necrosis factor-alpha remained undetectable.
Pretreatment with anti-tumor necrosis factor-alpha antibodies or rolipram attenuated lung injury, reversed tissue hypoxia, and blocked the upregulation of interleukin-1beta, interleukin-6, cytokine-induced neutrophil chemoattractant, and E-selectin mRNAs.

Cite This Study

Rabinovici et al. (1996) studied this question.

synapsesocial.com/papers/6a9539149c5cb11ee625e113 https://doi.org/10.1161/01.res.78.2.329

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Implication

Preclinical study demonstrates that local TNF-alpha mediates interleukin-2-induced lung injury in rats, highlighting potential therapies to reduce immunotherapy toxicity.

Locally Produced Tumor Necrosis Factor-α Mediates Interleukin-2Induced Lung Injury

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Implication

Key Points

Cite This Study

Locally Produced Tumor Necrosis Factor-α Mediates Interleukin-2Induced Lung Injury

Discussion

Member takes

Implication

Key Points

Cite This Study

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