| Interleukin-2 (IL-2) is one of the most thoroughly studied signaling molecules of theimmune system. Human IL-2 consists of a single peptide chain of 133 amino acids giving rise to a molecular weight of 15.42Kda. The integrity of the disulfide bond is crucial for the bioactivity of the cytokine whereas glycosylation does not appear to be essential. Biological effects of IL-2 are mediated through binding to specific IL-2 receptor (IL-2R) complexes. Three IL-2R proteins, a , P and Y, partly shared by other cytokine receptors are molecularly identified by now, but functional receptor complexes may contain associated proteins. The trimeric a 0 y combination represents the functional high-affinity IL-2R complex. IL-2 plays a pivotal role as an auto-paracrine growth factor for the activation and clonal expansion of effector T cells following an antigen challenge. IL-2 also exerts functions in the differentiation and activation of B cells, natural and lymphocyte-activated killer cells, neutrophils, monocytes and macrophages and thus participates in the initiation and regulation of both cellular as well as humoral defense mechanisms. As an immune regulator, IL-2 is clinically applied in the therapy of carcinoma. Unfortunately, administration of IL-2 can cause many side effects, including hypotension, arrhythmias, and vascular leak syndrome.In the normal brain, the IL-2/IL-2R system localizes mainly to the hippocampal formation, hypothalamus, cerebellum, frontal cortex, striatum, and septum and locus coeruleus. At the cellular level, both neurons and glial cells appear to be able to synthesize IL-2 and IL-2Rproteins. It was found that IL-2 could pass cross the intact blood-brain-barrier. In the centralnervous system, IL-2, as a neuroregulatory cytokine, supports the survial of cultured neurons and oligodendrocytes, and modulates the firing activity of neurons as well as the release of various neurotransmitters and neuropeptides. IL-2 can activate the hypothalamic-pituitary-adrenal axis and inhibit the hypothalamic-pituitary-thyroid and gonadal axis. IL-2 modulates the release of several hypothalamic and pituitary peptides, such as Met-enkephalin, 9 -endorphin, prolactin, luteinizing hormone, follicle-stimulating hormone, thyrotropic hormone, growth hormone, adrenocorticotropic hormone, corticotropin releasing factor, arginine vasopressin and somatostain. IL-2 also plays a modulatory role in cholinergic transmission in the hippocampus. Recently it was reported that intravenous IL-2 could reduce left ventricular ejection fraction. Little is known about cardiovascular response by central administration of IL-2.The purpose of the present study was to investigate the cardiovascular response caused by intracerebroventricular injection of IL-2 and explores the underlying mechanism. Arterial pressure and mean arterial pressure (MAP) were measured by cannulation of femoral artery and electrocardiogram was recorded by MedLab system. The intracerebroventricular microinjection of drugs into the lateral ventricle was employed.The rats were randomly divided into following groups. (1) Group IL-2: dose response of ICV IL-2 (500, 1000 and 1500 u/3ul (n=7, 7 and 6, respectively). (2) Group control: ICV 0.9% saline (n=8). (3) Group naloxone: ICV IL-2 1500u/3ul following pretreatment with naloxone 4ug/10ul (n=8). (4) Group atropine: ICV IL-2 1500u/3ul following pretreatment with atropine lOug/lOul (n=6). (5) Group phentolamine: ICV IL-2 1500u/3ul following pretreatment with phentolamine 10ug/10|il(n=6).The results showed that ICV injection of IL-2 at 500 and 1000u/3nl did not significantly affect the cardiovascular response but IL-2 at 1500u/3ul elevated MAP and HR. The response reached its maximum level 10 minutes after the injection and last 10 minutes, with the increases of MAP and HR to 9.80?. 80 mmHg 25?.53 beats/min respectively (PO.05). Pretreatmentwith naloxone (4u.g/10ul) blocked the IL-2 induced cardiovascular response. Pretreatment with4atropine (10ug/10u.l) blocked the elevation of bloo... |
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