FDA licensure of neumega&amp;reg; to prevent severe chemotherapy&amp;hyphen;induced thrombocytopenia

Kaye, James A.

doi:10.1002/stem.5530160724

Cited by 51 publications

(42 citation statements)

References 52 publications

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“…It also enhances antigen-specific antibody responses, increases the plasma concentration of acute-phase proteins, and inhibits lipoprotein lipase activity (7). Clinically, owing to its thrombopoiesis effect, recombinant human IL-11 is now used for the treatment of thrombocytopenia (8,9). IL-11 also participates in the regulation of bone cell proliferation and differentiation (10) and may have potential as a therapy for osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model

Tamura¹,

Kohno²,

Mohri³

et al. 2018

Ann. Cardiothorac. Surg.

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Background: Previously, we have demonstrated the cardioprotective effect of interleukin (IL)-11 in animal models of acute coronary syndrome. In this study, we sought to evaluate its cardioprotective potential during prolonged hypothermic global ischemia and subsequent reperfusion using a rat heart donor model.Methods: IL-11 was administered intravenously 10 minutes before harvesting the rat heart. The hearts were preserved in cold (4 ℃) Krebs-Henseleit buffer for 6 hours, and then attached to a Langendorff perfusion apparatus and reperfused with an oxygenated Krebs-Henseleit solution containing IL-11.Normal saline was used instead of IL-11 in the control group. Functional recovery of the reperfused heart was observed by using a left ventricular balloon. Myocardial cell injury was quantified by measuring the biomarkers collected from the coronary effluent. Apoptotic cells were identified and counted using the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) staining technique.Results: IL-11 administration improved myocardial function after 6 hours of cold ischemia. Although there were no significant differences in any of the baseline-measured values between the two groups, left ventricular developed pressure (LVDP) and changes in left ventricular pressures (dP/dt) were significantly higher in the IL-11 group at 120-minute reperfusion. The number of TUNEL-labeled cardiomyocytes was also significantly smaller in the IL-11 group. Conclusions:The administration of IL-11 showed a significant recovery of cardiac contractile function after 6 hours of cold ischemia. Our data suggest that it may have significant therapeutic potential for maintaining the functional viability of the heart exposed to prolonged hypothermic global ischemia.

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Section: Discussionmentioning

confidence: 99%

The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model

Tamura¹,

Kohno²,

Mohri³

et al. 2018

Ann. Cardiothorac. Surg.

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“…IL-11 was isolated as a cytokine that stimulates the proliferation of an IL-6-dependent plasmacytoma cell line (65). IL-11 exhibits thrombopoietic activity, and recombinant human IL-11 is clinically used for thrombocytopenia (66,67). In contrast to IL-6, IL-11 exhibits rather anti-inflammatory activity against chronic inflammatory diseases such as Crohn's disease (68).…”

Section: Clinical Perspectivementioning

confidence: 99%

Glycoprotein 130 Cytokine Signal as a Therapeutic Target Against Cardiovascular Diseases

et al. 2011

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Abstract. Postnatal cardiomyocytes have only limited capacity of proliferation. Therefore, the myocardium is intrinsically equipped with cardioprotective machineries and protects itself from pathological stresses. One of the most important cardioprotective systems is the signal network of autocrine/paracrine factors, including neurohumoral factors, growth factors, and cytokines. In this review, we focus on the roles of interleukin-6 (IL-6) family cytokines, also known as glycoprotein 130 (gp130) cytokines, in cardioprotection. These cytokines make a complex with their specific cytokine receptor α-subunits. The cytokine-receptor α-subunit complex binds to gp130, a common receptor of the IL-6 family, followed by the activation of JAK/STAT, ERK, and PI3 kinase/Akt pathways. In cardiomyocytes, signals through gp130 promote cell survival and angiogenesis through the JAK/STAT pathway. Activation of gp130 in cardiac stem cells induces their endothelial transdifferentiation, leading to neovascularization. Recently, accumulating evidence has revealed that altered JAK/STAT activity is associated with heart failure, suggesting that the JAK/STAT pathway is a therapeutic target against cardiovascular diseases. Interestingly, activation of the JAK/STAT pathway with interleukin-11 (IL-11) exhibits preconditioning effects in ischemia/reperfusion model. Moreover, IL-11 treatment after coronary ligation prevents cardiac remodeling through the JAK/STAT pathway. Since IL-11 is used for patients with thrombocytopenia, we propose that IL-11 is a candidate cytokine clinically available for cardioprotection therapy.

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“…The specificity of our mutational scheme (as demonstrated in N T -3N) has overcome this limitation, leading to a modified interleukin with enhanced biological activity. In principle, the favorable properties of this new variant would seem suitable to replace the currently administered recombinant (non-glycosylated) hIL-11 in the treatment of severe thrombocytopenia (7)(8)(9).…”

Section: Non-core Region Modulates Hil-11mentioning

confidence: 99%

“…Moreover, hIL-11 is a medically relevant protein of clinical potential. In particular, recombinant hIL-11 (oprelvekin) has been authorized by the FDA (Food and Drug Administration) to treat adult patients following myelosuppresive chemotherapy to prevent severe thrombocytopenia (7)(8)(9).…”

mentioning

confidence: 99%

Non-core Region Modulates Interleukin-11 Signaling Activity

Yanaka

Sano

Naruse

et al. 2011

Journal of Biological Chemistry

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FDA licensure of neumega® to prevent severe chemotherapy&hyphen;induced thrombocytopenia

Cited by 51 publications

References 52 publications

The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model

The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model

Glycoprotein 130 Cytokine Signal as a Therapeutic Target Against Cardiovascular Diseases

Non-core Region Modulates Interleukin-11 Signaling Activity

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