Interleukin-la Reduces the Severity of the Vascular Leak Syndrome Produced by Interleukin-2 and Interleukin-2 Plus Interferon-a

Fujita, Shinsuke; Puri, Raj K.; Yu, Zu‐Xi; Travis, William D.; Yamaguchi, Maria; Ferrans, Víctor J.

doi:10.1177/019262339402200404

Cited by 10 publications

(6 citation statements)

References 46 publications

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“…Thirdly, unlike prior studies, edema and cell infiltration in stifle joint was observed, a change that has not been observed until now. The lesion observed in the stifle joint is suggested to be due to VLS (Fujita et al, 1994), although the reasons accounting for difference between our study and prior studies are unclear.…”

Section: Organs (G%)contrasting

confidence: 96%

“…Eosinophil ratio and WBC were considered secondary to the pharmacological action of IL-2. Because rhIL-2 stimulates immune responses and the release of cytokines that promote inflammation (Higuchi et al, 1991;Thompson et al, 1987;Kovacs et al, 1995;Gately et al, 1988;Fujita et al, 1994;Ettinghausen et al, 1985;Anderson et al, 1988;Anderson and Hayes, 1989), circulatory leukocyte levels may be increased.…”

Section: Organmentioning

confidence: 99%

“…Perivascular inflammatory cell infiltration was also prominent in the lung, primarily observed in connective tissues around the bronchioles. Inflammatory cell infiltration in the liver, lung, and stifle joint and increased cellularity in spleen were considered to be a result of the pharmacological action of rhIL-2, because rhIL-2 stimulates immune responses, including the activation of natural killer cells, the release of cytokines promoting inflammation, and leakages of inflammatory cells into the tissue (Higuchi et al, 1991;Thompson et al, 1987;Kovacs et al, 1995;Gately et al, 1988;Fujita et al, 1994;Ettinghausen et al, 1985;Anderson et al, 1988;Anderson and Hayes, 1989). As decreased cellularity was observed in only thymus, we suggest two possibilities as follow.…”

Section: Organmentioning

confidence: 99%

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A four-week repeated study of intravenous toxicity of recombinant human interleukin-2 in Sprague–Dawley rats

Lee¹,

Kim²,

Kim³

et al. 2012

Regulatory Toxicology and Pharmacology

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Section: Organs (G%)contrasting

confidence: 96%

Section: Organmentioning

confidence: 99%

Section: Organmentioning

confidence: 99%

See 1 more Smart Citation

A four-week repeated study of intravenous toxicity of recombinant human interleukin-2 in Sprague–Dawley rats

Lee¹,

Kim²,

Kim³

et al. 2012

Regulatory Toxicology and Pharmacology

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“…12,62 These abnormalities could be the result of an increased permeability of vascular capillaries accompanying chronic hypoxia, infection and inflammation states, release of inflammatory mediators, and a long-lasting overload of cardiovascular and respiratory systems due to the narrowing airways and small pulmonary arteries of these children. 69 In addition, IFN-␣ administered in combination with IL-2 produced more severe vascular leakage (also highly related to the dose of IFN-␣), causing perivascular and intraalveolar edema and increased lung water weight, [69][70][71] the abnormalities presenting at autopsy of SIDS victims as pulmonary congestion and edema. 69 In addition, IFN-␣ administered in combination with IL-2 produced more severe vascular leakage (also highly related to the dose of IFN-␣), causing perivascular and intraalveolar edema and increased lung water weight, [69][70][71] the abnormalities presenting at autopsy of SIDS victims as pulmonary congestion and edema.…”

Section: Inflammatory Changes In the Respiratory And Gastrointestinalmentioning

confidence: 99%

Possible Pathomechanisms of Sudden Infant Death Syndrome

Prandota¹

2004

American Journal of Therapeutics

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Chronic hypoxia, viral infections/bacterial toxins, inflammation states, biochemical disorders, and genetic abnormalities are the most likely trigger of sudden infant death syndrome (SIDS). Autopsy studies have shown increased pulmonary density of macrophages and markedly more eosinophils in the lungs accompanied by increased T and B lymphocytes. The elevated levels of immunoglobulins, about 20% more muscle in the pulmonary arteries, increased airway smooth muscle cells, and increased fetal hemoglobin and erythropoietin are evidence of chronic hypoxia before death. Other abnormal findings included mucosal immune stimulation of the tracheal wall, duodenal mucosa, and palatine tonsils, and circulating interferon. Low normal or higher blood levels of cortisol often with petechiae on intrathoracic organs, depleted maternal IgG antibodies to endotoxin core (EndoCAb) and early IgM EndoCAb triggered, partial deletions of the C4 gene, and frequent IL-10-592*A polymorphism in SIDS victims as well as possible hypoxia-induced decreased production of antiinflammatory, antiimmune, and antifibrotic cytokine IL-10, may be responsible for the excessive reactions to otherwise harmless infections. In SIDS infants, during chronic hypoxia and times of infection/inflammation, several proinflammatory cytokines are released in large quantities, sometimes also representing a potential source of tissue damage if their production is not sufficiently well controlled, eg, by pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP). These proinflammatory cytokines down-regulate gene expression of major cytochrome P-450 and/or other enzymes with the specific effects on mRNA levels, protein expression, and enzyme activity, thus affecting metabolism of several endogenous lipophilic substances, such as steroids, lipid-soluble vitamins, prostaglandins, leukotrienes, thromboxanes, and exogenous substances. In SIDS victims, chronic hypoxia, TNF-alpha and other inflammatory cytokines, and arachidonic acid (AA) as well as n-3 polyunsaturated fatty acids (FA), stimulated and/or augmented superoxide generation by polymorphonuclear leukocytes, which contributed to tissue damage. Chronic hypoxia, increased amounts of nonheme iron in the liver and adrenals of these infants, enhanced activity of CYP2C9 regarded as the functional source of reactive oxygen species (ROS) in some endothelial cells, and nicotine accumulation in tissues also intensified production of ROS. These increased quantities of proinflammatory cytokines, ROS, AA, and nitric oxide (NO) also resulted in suppression of many CYP450 and other enzymes, eg, phosphoenolpyruvate carboxykinase (PEPCK), an enzyme important in the metabolism of FA during gluconeogenesis and glyceroneogenesis. PEPCK deficit found in SIDS infants (caused also by vitamin A deficiency) and eventually enhanced by PACAP lipolysis of adipocyte triglycerides resulted in an increased FA level in blood because of their impaired reesterification to triacylglycerol in adipocytes. In ...

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“…IL-2 and IFN administration can result in increased NO production and release [45]. Excessive vascular wall relaxation, vascular leakage and disrupted myocardial signalling pathways are potential consequences [46].…”

Section: Interleukinmentioning

confidence: 99%

Cardiotoxic mechanisms of cancer immunotherapy – A systematic review

Lobenwein

Kocher

Dobner

et al. 2021

International Journal of Cardiology

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Cancer immunotherapy is a success story of translational medicine that has led to improved survival in patients with different difficult-to-treat types of cancer, such as metastasized melanoma, non-small cell lung cancer or renal cell carcinoma. These novel therapeutic agents exert their antitumor effects by activating the patients' immune system against cancer cells. Immunotherapy can be divided into active agents, such as anti-tumour vaccines or adoptive T-cell transfer, and passive immunotherapies like monoclonal antibodies, checkpoint inhibitors, cytokine therapy, bispecific T-cell engagers. After initial experimental use, broad clinical application revealed a number of important cardiovascular side effects of immunotherapeutics, which limit treatment options and decrease patients' prognosis and quality of life. With the rising rate of new immunotherapeutics at a hand, the number of patients receiving cancer immunotherapy will constantly increase, resulting in improved long-term survival rates. This review aims to summarize available cancer immunotherapies, their mechanism of action, currently known cardiovascular toxicities and their treatment. Further optimization of patient care will depend on the combined efforts by oncologists, cardiologists and cardiac surgeons to identify patients at risk and the implementation of interdisciplinary screening and treatment strategies. It is therefore crucial to familiarize heart specialists with novel cancer therapeutics and their potential adverse effects.

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Interleukin-la Reduces the Severity of the Vascular Leak Syndrome Produced by Interleukin-2 and Interleukin-2 Plus Interferon-a

Cited by 10 publications

References 46 publications

A four-week repeated study of intravenous toxicity of recombinant human interleukin-2 in Sprague–Dawley rats

A four-week repeated study of intravenous toxicity of recombinant human interleukin-2 in Sprague–Dawley rats

Possible Pathomechanisms of Sudden Infant Death Syndrome

Cardiotoxic mechanisms of cancer immunotherapy – A systematic review

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