Therapeutic relevance of altered cytokine expression.
Therapeutic relevance of altered cytokine expression.
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DOI：
10.1006/cyto.2000.0827
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发表时间：
2001-04
期刊：
影响因子：
3.8
通讯作者：
Kenneth M. Kulmatycki;Fakhreddin Jamali
中科院分区：
文献类型：
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作者：
Kenneth M. Kulmatycki;Fakhreddin Jamali
细胞因子及其受体具有多种生理功能。这些介质浓度的改变与各种痛苦有关。例如，细胞因子的过度表达与药物浓度和活性的改变有关。与健康对照组相比，在患有各种炎症性疾病的人类和实验动物中观察到更高浓度的心血管药物。有趣的是，观察到的较高浓度的药物，如心得安和维拉帕米，并没有与增加效果相关。事实上，可以观察到对这些心血管药物的反应降低，这表明细胞因子介导的受体下调。细胞因子浓度的增加也与用于治疗其他疾病的药物反应降低有关，如艾滋病、哮喘和精神疾病。这种在细胞因子浓度改变时对药物的反应降低与老年人群尤其相关，因为与年轻人相比，老年人群患多种疾病的几率更高，各种细胞因子的浓度也更高。此外，炎症状态及其伴随的细胞因子过度表达的增加被认为是心肌梗死和心绞痛治疗失败的主要决定因素。因此，细胞因子浓度的改变可能会影响药物治疗的疗效，导致治疗失败。
Cytokines and their receptors have numerous physiological functions. Altered concentrations of these mediators are associated with various afflictions. For example, over-expression of cytokines has been associated with altered drug concentrations and activity. Greater concentrations of cardiovascular drugs have been observed in humans and laboratory animals with various types of inflammatory disorders compared to healthy controls. Interestingly, the observed higher concentrations of drugs such as propranolol and verapamil have not been associated with increased effects. Indeed, reduced response to these cardiovascular drugs is observed, suggestive of cytokine-mediated downregulation of receptors. Increased cytokine concentrations have also been associated with decreased response to drugs used in treatment of other disorders such as AIDS, asthma and psychiatric diseases. This reduced response to drug in the presence of altered cytokine concentrations is especially relevant to the elderly population which has a greater incidence of multiple diseases and elevated concentrations of various cytokines compared to younger individuals. Furthermore, inflammatory conditions and their accompanied increased over-expression of cytokines are suggested to be the main determinants of therapeutic failure in myocardial infarction and angina. Therefore, altered cytokine concentrations may influence therapeutic outcomes of pharmacotherapy and result in treatment failure.