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葡萄糖、胰岛素和钾在免疫学与肿瘤学中的意义:一种新的免疫模型

The significance of glucose, insulin and potassium for immunology and oncology: a new model of immunity.

作者信息

Hill Albert F, Polvino William J, Wilson Darcy B

机构信息

Hill Medical, LLC, Denver, CO 80220-1644, USA.

出版信息

J Immune Based Ther Vaccines. 2005 Aug 19;3:5. doi: 10.1186/1476-8518-3-5.

Abstract

BACKGROUND

A recent development in critical care medicine makes it urgent that research into the effect of hormones on immunity be pursued aggressively. Studies have demonstrated a large reduction in mortality as a result of infusion with glucose, insulin and potassium. Our work in the oncology setting has led us to propose that the principal reason for such an effect is that GIK stimulates lymphocytes to proliferate and attack pathogens, sparing the patient the stress of infection. That suggestion is based on a new model of immunity that describes the effect of hormones on lymphocytes. We hypothesized that the application of glucose, insulin, thyroid and potassium would awaken inert tumor infiltrating lymphocytes to destroy the tumor.

METHODS

The antitumor effect of a thyroxine, glucose, insulin, and potassium (TGIK) combination was studied in a series of controlled experiments in murine models of tumor progression to assess the biologic activity of the formulation, the effect of route of administration, the effect on tumor type, and the requirement for insulin in the TGIK formulation.

RESULTS

Melanoma and colon tumors inoculated with TGIK were significantly reduced in size or retarded in growth compared to controls injected with saline. I.P. and I.M. injections showed that the formulation had no effect systemically at the doses administered.

CONCLUSION

We conclude that TGIK has anti-tumor activity when administered intratumorally, probably by stimulating lymphocytes to attack tumors. This is similar to the effect of GIK on reducing sepsis in critical care patients. We suggest that when GIK is administered exogenously, it restores immune competence to the critically ill or cancer patient and causes destruction of pathogens or tumors, while endogenous resources are devoted to repair. This implies that hormonal therapy may be useful in treating various other pathologies involving immune suppression, as well as malignancies. We also propose research that could bring resolution of the controversy over mechanism and point the way to new therapeutic strategies for numerous diseases including chronic infections and auto-immune diseases.

摘要

背景

重症监护医学领域的一项最新进展使得积极开展关于激素对免疫作用的研究变得刻不容缓。研究表明,输注葡萄糖、胰岛素和钾可使死亡率大幅降低。我们在肿瘤学领域的工作促使我们提出,产生这种效果的主要原因是葡萄糖 - 胰岛素 - 钾(GIK)刺激淋巴细胞增殖并攻击病原体,从而使患者免受感染的压力。这一观点基于一种描述激素对淋巴细胞作用效果的新免疫模型。我们假设应用葡萄糖、胰岛素、甲状腺素和钾会唤醒惰性肿瘤浸润淋巴细胞以破坏肿瘤。

方法

在一系列肿瘤进展的小鼠模型对照实验中,研究了甲状腺素、葡萄糖、胰岛素和钾(TGIK)组合的抗肿瘤作用,以评估该制剂的生物活性、给药途径的影响、对肿瘤类型的影响以及TGIK制剂中胰岛素的需求。

结果

与注射生理盐水的对照组相比,接种TGIK的黑色素瘤和结肠肿瘤大小显著减小或生长受到抑制。腹腔注射和肌肉注射表明,在所给剂量下该制剂无全身作用。

结论

我们得出结论,TGIK瘤内给药时具有抗肿瘤活性,可能是通过刺激淋巴细胞攻击肿瘤。这类似于GIK在降低重症监护患者败血症方面的作用。我们认为,外源性给予GIK时,它能恢复重症患者或癌症患者的免疫能力,导致病原体或肿瘤被破坏,同时将内源性资源用于修复。这意味着激素疗法可能有助于治疗涉及免疫抑制的各种其他病症以及恶性肿瘤。我们还提议开展相关研究,以解决关于机制的争议,并为包括慢性感染和自身免疫性疾病在内的众多疾病指明新的治疗策略方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4bd/1201164/4eee0c6930b7/1476-8518-3-5-1.jpg

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