Immunodeficiency in ESRD-patients is linked to altered IL-2 receptor density on T cell subsets.

The interdependence of blunted T cell proliferation induced by anti-CD3 monoclonal antibodies (mAb) and the preactivation of T lymphocytes (CD25+) in ESRD patients was investigated in this study. We focused on the density of IL-2 (CD25) receptors [IL-2R] on the lymphocyte surface rather than enumeration of IL-2R positive cells. The effect of exogenous IL-2 on these parameters was also tested. Blunted T lymphocyte proliferation induced by anti-CD3 mAb is only partially corrected by addition of exogenous IL-2 after 24 hrs. Freshly isolated uremic CD4 T cells show higher percentage of IL-2 positive cells and a higher IL-2R density on the cell surface compared to controls. However, after anti-CD3 mAb stimulation the number of IL-2R positive cells and IL-2R density in CD4 T subset was significantly lower than in samples from normal donors. Exogenous IL-2 had no influence on IL-2R expression on CD4 cells in uremic patients. On the other hand, following anti-CD3 mAb stimulation uremic CD8 cells reveal more IL-2R positive cells with higher IL-2R density than in controls. Moreover, exogenous IL-2 enhance IL-2R expression and density on uremic CD8 cells more than in controls. Our results suggest that the blunted T cell proliferation in ESRD patients might result from (a) preactivation of CD4 T cells, (b) diminished response of uremic CD4 T cells to IL-2, and (c) higher suppressor cells activity.     

IL-17R在韦格纳肉芽肿患者外周血免疫细胞的表达

目的检测韦格纳肉芽肿(WG)患者外周血免疫细胞特别是B淋巴细胞和浆细胞上IL-17受体(IL-17R)的表达有无异常。方法流式细胞仪检测正常人(HC)及WG患者外周血免疫细胞表面IL-17R蛋白的表达。结果 IL-17R在WG患者外周血中性粒细胞(PMN)、单核细胞(Mono)、总淋巴细胞(Lym)上的表达与正常人无显著差异,但在B淋巴细胞(CD19+CD20+)(P<0.05)和浆细胞(CD19+CD38+)(P<0.05)上的表达显著高于正常人;活动期与非活动期患者、环磷酰胺(Cyc)和甲氨蝶呤(MTX)治疗组患者IL-17R的表达无显著差异。结论 IL-17R在WG患者外周血B淋巴细胞和浆细胞上的表达显著升高,但在中性粒细胞和单核细胞上的表达无明显异常。     

The immune function injury and its mechanism in drug abuser

Objective:To explore the immune function injury and its mechanism in drug abuser.Methods:The immune function changes in 50 drug abusers were compared with normal healthy populations by detection of the indexes of subgroups of Th cells,transformation rate of lymphocytes,IgA,IgM,IgG,IgE,compliment C3,C4,IL-1,Il-2,IL-6 TNF and NO.Result:In peripheral blood the percentage of Th1 cell,transformation rate of lymphocyte,IgA,IgM,IgG,IgE content,compliment C4,C4,IL-1,IL-2,IL-6,and TNF levels were significantly lower than normal (P&;lt;).01).The value of Th1/Th2 was lower than normal as well(P&;lt;0.05).NO content was significantly higher than normal (P&;lt;0.001).Conclusion:The mechanism of immune function injury in drug abuser might be correlative to direct injury of drugs and their inhibition effect on the thymus-hypothalamus-hypophysis-adrenal axis.     

缺铁性贫血合并反复呼吸道感染患儿细胞免疫功能观察

目的：测定６３例缺铁性贫血（ＩＤＡ）合并反复呼吸道感染（ＲＲＩ）患儿外周血白细胞介素２（ＩＬ－２）活性、血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平和Ｔ淋巴细胞亚群，并分析它们之间的相关性。方法：ＩＬ－２活性和ｓＩＬ－２Ｒ水平测定分别采用ＭＴＴ法和双抗体夹心法，Ｔ淋巴细胞亚群测定采用ＡＰＡＡＰ法。结果：ＩＬ－２活性，ＣＤ３＋、ＣＤ４＋细胞百分率和ＣＤ４＋／ＣＤ８＋细胞比值均显著低于对照组（Ｐ均＜０．０１），而ｓＩＬ－２Ｒ水平显著高于对照组（Ｐ＜０．０１），ＣＤ８＋细胞百分率无明显变化。结论：ＩＤＡ合并ＲＲＩ患儿细胞免疫功能低下且紊乱。     

The role of interleukin-10 in systemic inflammatory response syndrome with sepsis

This study was performed to demonstrate the role of interleukin (IL)-10, especially in systemic inflammatory response syndrome (SIRS) patients. In clinical observations, levels of serum tumor necrosis factor-α (TNF) and IL-10 increased in SIRS patients (TNF, n=43; IL-10, n=33), and they increased more in the patients with organ failure (n=22) than in patients without organ failure (n=24), (P<0.01). In mice, serum TNF and IL-10 began to increase at 1 hour after injection with 4mg/kg of lipopolysaccharide (LPS) and reached a maximum at 2 hours. However, the serum level of TNF decreased to an undetectable level at 6 hours, while a significant amount of IL-10 remained in serum. The TNF elevation induced by LPS injection was inhibited by pretreatment with 200 ng of IL-10 (P<0.1 in serum,P<0.05 in bronchoalveolar lavage fluid). Neutrophil reduction induced by LPS injection was also inhibited by pretreatment with 1 μg of IL-10. On human neutrophils the expression of adhesion molecules LFA-1 and MAC-1 that resulted from in vitro incubation with TNF were suppressed by the addition of IL-10 supplement. The expression of TNF receptors on the surface of human neutrophils as a result of LPS loading was also suppressed by IL-10 supplement. IL-10 seems have a protective function in the progress to organ failure in SIRS patients with sepsis. IL-10 suppresses TNF production and inhibits the expression of adhesion molecules and TNF receptors on neutrophils.     

Systemic interleukin-1 α and interleukin-2 secretion in response to acute stress and to corticotropin-releasing hormone in humans*

Abstract Acute stress results in activation of the hypothalamic-pituitary-adrenal (HPA) axis. ACTH and cortisol secretion is stimulated by corticotropin-releasing hormone (CRH). It has also been shown that activation of the HPA axis during stress is accompanied by changes in the immune response. However, little is known about the influence of acute stress on the release of cytokines such as inteleukin-1 (IL-1) or interleukin-2 (IL-2). In this study, we determined serum IL-1 α and IL-2 levels in 19 patients undergoing the acute stress of angioplasty for coronary artery disease. A second protocol was devised to determine serum IL-1 α and IL-2 concentrations as well as lymphocyte subpopulations in 10 normal volunteers receiving 1 μ kg^-1 human CRH intravenously. Finally, IL-1 α concentrations were measured in CRH-incubated mononuclear cell (MNC) and monocyte cultures. In response to the stress of angioplasty, ACTH and cortisol as well as IL-1 α and IL-2 concentrations were clearly above baseline levels (IL-1 α, mean ± SEM, baseline: 1·39 ± 0·34 ng ml^-1, after angioplasty: 2·64 ± 0·73 ng ml^-1, P < 0·05; IL-2, baseline: 1·2 ± 0·13 ng ml^-1, after angioplasty: 2·8 ± 1·14 ng ml, P < 0·05). A similar pattern was obtained in normal subjects in response to CRH (IL-1 α, baseline: 0·8 ± 0·2 ng ml^-1, after angioplasty: 3·7 ± 1·4 ng ml^-1, P < 0·05; IL-2, baseline: 1·9 ± 0·4 ng ml^-1, after angioplasty: 5·4 ± 2·2 ng ml^-1, P < 0·02). The percentage of IL-2 receptor-positive lymphocytes rose from 3·9 ± 1·2% to 6·2 ± 1·6% (P < 0·05), the relative number of CD-3 lymphocytes rose from 74·5 ± 1·6% to 78·3 ± 2·0% (P < 0·05). No significant changes were observed in the number of CD-4, CD-8, natural killer and B cells. In vitro, IL-1 α concentrations in cultures containing CRH were not significantly different from control cultures. Our data demonstrate significant activation of the HPA axis and secretion of IL-1 α and IL-2 in response to both angioplasty and CRH. Furthermore, CRH administration resulted in activation of the cellular immune system (indicated by an increase in IL-2 receptor positive lymphocytes). Our in vitro data suggest that CRH may not directly act on blood mononuclear cells to induce IL-1 α release or, alternatively, sources other than blood mononuclear cells may account for the elevated IL-1 α levels observed in vivo. We conclude that CRH may play a major role in neuroendocrine-immune interactions during acute stress.     

Very late activation antigens on rheumatoid synovial fluid T lymphocytes. Association with stages of T cell activation.

Lymphocytes from the synovial fluid of eight out of eight rheumatoid arthritis (RA) patients had elevated very late activation antigen-1 (VLA-1) expression (10-36% positive cells), whereas peripheral blood lymphocytes (PBL) from RA patients and healthy controls had low VLA-1 expression (0-6% positive cells). During 1-2 wk of in vitro culture, VLA-1 increased on synovial fluid cells but remained low on PBL. In comparison, the interleukin 2 receptor (IL-2 R) was less prominent than VLA-1 on fresh synovial fluid cells, did not increase on cultured synovial fluid T cells, but did increase greatly on cultured PBL. The mitogen PHA reversed or prevented the appearance of VLA-1+, IL-2 R- synovial fluid cells during in vitro culture, thus giving IL-2 R+, VLA-1- cells. These results emphasize that VLA-1+ SF cells are different from resting cells or IL-2 R+ activated PBL T cells, and VLA-1 on synovial fluid T cells may be incompatible with mitogen stimulation. In addition, the VLA-2 heterodimer (165,000/130,000 relative molecular mass [Mr]) was regulated opposite to the VLA-1 heterodimer (130,000/210,000 Mr) on synovial lymphocytes, and thus the VLA-1/VLA-2 ratio is another indicator of the stage of T cell activation.     

Expression and release of IL-2 receptor and production of IL-2 by activated T lymphocyte subsets.

T lymphocyte subsets differ in expression of cell surface antigen and functional properties. Both CD4+ and CD8+ subsets express interleukin-2 receptor (IL-2R) following their activation in vitro. In the present investigation T lymphocyte subsets were activated by different mitogens and IL-2R expression was enumerated on these stimulated subsets. Peripheral blood mononucleated cells (PBMC) were stimulated with phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) and then stained with anti-CD4 or anti-CD8 antibodies conjugated with fluorescein isothiocyanate and anti-IL-2R monoclonal antibody conjugated with phycoerythrin using a direct immunofluorescence technique. The percentage of IL-2R positive lymphocytes was enumerated by flow cytometry. The results showed that mitogen activated lymphocytes expressed variable degrees of IL-2R which were significantly higher than the control. 53% of CD4+ lymphocytes and 28% of CD8+ expressed IL-2R following PHA stimulation in vitro. Similarly, 47% of CD4+ lymphocytes and 23% of CD8+ lymphocytes expressed IL-2R following PWM stimulation. The present study also revealed that the release of soluble IL-2R (sIL-2R) and IL-2 production in supernatant from cultured PBMC varied with different mitogen stimulation. Using the same concentration of PHA and PWM as used to study IL-2R expression, higher activity of sIL-2R was detected in PHA stimulated lymphocytes as compared to PWM treated lymphocytes. However, IL-2 production was more in culture medium from PMW treated PBMC. Thus, there was a significant correlation between the cellular and soluble IL-2R but the production of IL-2 from activated PBMC cells had no good correlation with either the cellular IL-2R expression or the release of sIL-2R.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of Effects of Low-Flow Sevoflurane and Desflurane Anesthesia on Neutrophil and T-Cell Populations

BackgroundNumerous transient effects of anesthesia on postoperative immune status have been documented in the literature.ObjectiveThis study was performed to test the hypothesis that the effects on neutrophil and T-cell populations differ with use of low-flow sevoflurane- and desflurane-induced anesthesia during abdominal surgery.MethodsFifty adult patients (American Society of Anesthesiologists physical status I or II) aged 20 to 60 years were recruited for the study. Patients were randomly assigned to one of two study groups. Anesthesia was induced using fentanyl, propofol, and vecuronium. After intubation, patients in group 1 received sevoflurane, oxygen, and nitrous oxide at a flow rate of 6 L/min, and those in group 2 received desflurane, oxygen, and nitrous oxide at a flow rate of 6 L/min. Ten minutes after induction of anesthesia, the flow rate was decreased to 1 L/min in both groups. Total leukocyte, lymphocyte, and neutrophil counts, percentage of T helper lymphocytes (CD4), cytotoxic T lymphocytes (CD8), natural killer lymphocytes, and active T lymphocyte, CD4/CD8 ratio, and plasma cortisol values were assessed before and at 2 and 24 hours after induction of anesthesia.ResultsIn the desflurane group, at 2 hours after induction of anesthesia, a significant decrease was observed in the lymphocyte count, percentage of CD4 cells, and CD4/CD8 ratio, and a significant increase was noted in the neutrophil count and percentage of CD8 cells (P < 0.05). At 24 hours after induction of anesthesia, a significant increase was observed in the leukocyte and neutrophil counts, percentage of CD4 cells, and CD4/CD8 ratio (P < 0.05). There was no change in the other parameters studied. In the sevoflurane group, a significant decrease was observed in the lymphocyte count and percentage of natural killer cells. In addition, a significant increase was noted in the leukocyte and neutrophil counts at 24 hours after induction of anesthesia (P < 0.01). The increase in the neutrophil count in the desflurane group compared with that in the sevoflurane group was statistically significant (P < 0.05).ConclusionsWith use of the low-flow anesthesia technique, compared with desflurane, sevoflurane exerts minimal effects on neutrophil and T-cell populations, which supports our hypothesis.     

Early alterations in the number of circulating lymphocyte subpopulations and enhanced proinflammatory immune response during opioid-based general anesthesia

The balance between proinflammatory and anti-inflammatory processes is of key importance in the reaction of the body to infection, injury, and surgical trauma. Drugs commonly used in anesthesia and intensive care may modulate immunological reactions by influencing intercellular communication through modification of cytokine response and fluctuation of peripheral immune cells such as natural killer (NK) cells, B cells, and T lymphocyte subpopulations (CD4+ and CD8+ cells). To examine the effects of general anesthesia with the hypnotic agent propofol and the opioid fentanyl, 30 patients undergoing minor elective orthopedic surgery were studied before and 20 min after application of the anesthetic drugs, but before the start of surgery. We found a significant enhancement of TNF-alpha and IL-1beta release in lipopolysaccharide (LPS)-stimulated whole blood cultures after induction of anesthesia. Similar results were observed with interferon-gamma (IFN-gamma) in cultures stimulated with phytohemagglutinin (PHA). Conversely, synthesis of the anti-inflammatory cytokine interleukin 10 (IL-10) decreased significantly in LPS-stimulated cultures. During general anesthesia, we found a decrease of circulating lymphocytes, characterized by a significant increase in the percentage of T lymphocytes in favor of CD4+ cells, increased B lymphocytes, and a significant decrease of NK cells. These data suggest that anesthesia with propofol and fentanyl promotes proinflammatory immune responses and influences peripheral lymphocyte composition in patients, which may subsequently affect pathophysiological processes during opioid-based anesthesia.     

微小核糖核酸155对不稳定性心绞痛患者CD4+T淋巴细胞的调控作用

目的 探讨微小核糖核酸-155 (miRNA-155)对不稳定性心绞痛(UAP)患者外周血CD4 +T淋巴细胞的调控作用,从而阐明miRNA-155在UAP发病中的作用机制。方法 选取住院的UAP患者21例,同时以疑似不典型冠心病症状而冠脉造影正常的住院患者18例作为对照组。采用实时定量PCR检测外周血CD4+T淋巴细胞miRNA-155表达水平,酶联免疫法检测血清干扰素-γ(interferon-γ,IFN-γ)、白细胞介素4(interleukin-4,IL-4)表达水平。免疫磁珠法分选10例UAP患者外周血CD4 +T淋巴细胞,将分离的细胞分为对照组、miRNA-155组和miRNA-155抑制物组。对培养的细胞进行干预后,流式细胞术检测辅助性T细胞Th1和Th2数量,实时定量PCR及蛋白免疫印迹法检测IFN-γ受体α(interferon gamma receptor alpha,IFN-γRα)、T细胞表达T盒(T-box expressed in T cells,T-bet)、GATA结合蛋白3(GATA-binding protein 3,GATA-3)的mRNA及蛋白表达,酶联免疫法检测细胞培养液上清IFN-γ、IL-4的表达。结果 UAP患者外周血CD4+T淋巴细胞miRNA-155与血清IFN-γ表达较对照组差异具有统计学意义(P＜0.01),且miRNA-155的表达与血清IFN-γ呈显著正相关(r=0.842,P＜0.01)。与对照组比较,体外培养CD4 +T淋巴细胞miRNA-155组Th1数量、T-bet mRNA及蛋白、培养液上清IFN-γ表达显著增加,IFN-γRα蛋白表达降低,差异具有统计学意义(均P ＜0.01);Th2数量、GATA-3、IFN-γRα的mRNA、GATA-3蛋白表达及培养液上清IL-4无明显改变(均P＞0.05);miRNA-155抑制物可有效地阻断miRNA-155的上述作用。结论 miRNA-155主要通过影响Th1细胞的分化和功能,参与对CD4 +T淋巴细胞的调控,在UAP发病机制中具有重要的作用。     

Immune potential of lymph node-derived lymphocytes in uncontrolled hemorrhagic shock

The state of T cell immunity was evaluated in rats in early (1-4 h) hemorrhagic shock induced by a massive splenic injury. T cell subpopulations from treated and untreated shocked animals were tested by flow cytometry and the results were compared with healthy controls. A fall in CD4+ T lymphocyte and natural killer (NKR-P1+) cell number, marked decline in the T helper (CD4+) to T suppressor (CD8+) ratio, and decrease of interleukin-2 receptor (IL-2R) bearing cells in peripheral blood, mesenteric, and popliteal lymph nodes of rats was found in the early stages of hemorrhagic shock. The same phenotype profile was also revealed in lymphocytes of rats in hemorrhagic shock following massive splenic injury treated with Ringer's lactate. The number of TCRalpha beta and TCR-gamma delta positive cells, as well as the percentage of CD4 and CD8 positive cells in the thymus, was similar in all groups of rats. Culture of lymph node cells taken from rats following hemorrhage in the presence of 100 U/mL hrIL-2 resulted in a marked increase in the number of NKR-PI+ positive cells from 4.2% to 30.5% (P < 0.001). Magnet separated NKR-P1+ fractions lysed the allogeneic fibroblasts in the same manner as IL-2-activated NKR-P1 cells from the control rats. Popliteal lymph node (PLNi) CD8b+ lymphocytes from rats in hemorrhagic shock preinfected into the footpad with cytomegalovirus (CMV) 6 days prior to injury lost their ability to lyse the CMV-infected fibroblasts and protect the monolayer from CMV infection when compared with PLNi cells from control infected rats. The possible mechanisms for the observed cellular dysfunction following hemorrhage are discussed.     

Platelets in ulcerative colitis and Crohn's disease express functional interleukin-1 and interleukin-8 receptors

Abstract Tissue and plasma concentrations of several cytokines are increased in patients with inflammatory bowel disease (IBD). Platelets play an important role in inflammation and circulate in an activated state in patients with IBD. This study assesses the expression of IL-8 and IL-1 receptors on the surface of platelets from patients with IBD using phycoerythrin (PE)-labelled recombinant human rhIL-1 β and rhIL-8 and flow cytometry. The percentage IL-1R expressing platelets (median and interquartile range IQR) in the IBD group was 8·7% (5·5–18·2) compared to 4·2% (2·3–6·1) in controls ( P = 0·02). The percentage IL-8R expressing platelets in the IBD group was 22·5% (16·5–27·9) and 9·2% (4·3–9·6) in controls ( P < 0·001). Furthermore, platelet IL-1R expression in patients with IBD was inversely related to the total daily dose of steroids ( r =–0·71, P < 0·01 linear regression analysis). Finally, platelet rich plasma from healthy controls was stimulated with rhIL-1 β and rhIL-8 and assessed for activation dependent expression of platelet aGPIIb/IIIa and CD62 (p-selectin, GMP-140). IL-1 β and IL-8 in vitro significantly and specifically activated the platelets. The surface membrane of platelets is able to express functional IL-1R and IL-8R, the expression of which is signficantly increased in IBD. Interleukin-1 β and IL-8 modulate platelet activation in vitro indicating a target role for platelet function in inflammation.     

Human appendix B cells naturally express receptors for and respond to interleukin 6 with selective IgA1 and IgA2 synthesis

Past studies have shown that freshly isolated human B cells from peripheral blood and tonsils do not express IL-6 receptors (IL-6R); however, mitogen or antigen activation of these B cells induces IL-6R and responsiveness to IL-6. In this study, we have shown that a high proportion of B cells enzymatically dissociated from human appendix, a gut-associated lymphoreticular tissue (GALT), expresses the IL-6R, and that recombinant human IL-6 induces significant increases in the number of Ig-producing cells. The recombinant human IL-6-induced increase in Ig-producing cells is restricted to the IgA isotype. Further, IgA2 is the major subclass; however, significant numbers of IgA1 producing cells are also seen. In contrast, human tonsillar and peripheral blood B cells express low levels of IL-6R, and exogenous IL-6 does not increase numbers of Ig-producing cells. When PBMC or tonsillar cells are stimulated with PWM, the former display an equal distribution of IgA1 and IgA2 secreting cells, while tonsillar B cells are mainly of the IgA1 subclass. The distribution of surface Ig-positive (sIg+) B cells in the appendix B cell population is sIgA+ greater than sIgG+ greater than sIgM+, and the sIgA+ B cells express higher levels of IL-6R when compared with sIgG+ or sIgM+ B cells. These studies show that human appendix contains B cell subsets that constitutively express IL-6R, and that a high proportion of these cells are committed to the IgA isotype. Furthermore, higher numbers of IL-6 responsive IgA2 B cells are present in the human appendix as compared to tonsils or PBMC.     

Suppressive activity of erythromycin in the expression of cytokine mRNA

We investigated the in vitro effects of erythromycin (EM) on the expression of mRNA for interleukin (IL)-1β, IL-8 and tumor necrosis factor (TNF)-α (inflammatory cytokines) in lipopolysaccharide (LPS)-stimulated human peripheral whole blood (PB) and peripheral blood mononuclear cells (PBMC). In LPS-stimulated PBMC, the expression of 3 cytokines (IL-1β, IL-8, TNFα) was significanttly (P<0.05) suppressed by pretreatment with EM at therapeutic doses. In PB, suppression of expression of IL-1β and TNFα was significant (P<0.05) at therapeutic doses, but IL-8 expression was only slightly suppressed. These results suggest that EM acts as an anti-inflammatory agent by suppressing the production and secretion of inflammatory cytokines by activated monocytes.     

How does interleukin-6 affect the membrane expressions of interleukin-6 receptor and gp130 and the proliferation of the human myeloma cell line OPM-2?

Interleukin-6 (IL-6) is a potent growth factor for the proliferation of multiple myeloma (MM), which accounts for 1-2% of all human cancers. In this study we investigated the effects of IL-6 in various doses on the following parameters in the human myeloma cell line OPM-2: membrane expression of IL-6 receptor (IL-6R) and gp130, proliferation of the tumour cells and the amount of the soluble IL-6 receptor (sIL-6R) in the supernatant. Additionally, we tested the same parameters with the immunomodulator Viscum album (VA) extract. The expression of surface IL-6R and gp130 was analysed by FACS, the measurements of proliferation using the BrdU incorporation during DNA synthesis, and the determination of sIL-6R in the supernatant by ELISA. OPM-2 cells proliferate spontaneously (doubling time: 48 h), IL-6-production was not detectable. The exogenous IL-6 upregulated its own receptor up to a mean of 180% of controls at 5 ng/ml (P < 0.001), higher or lower doses were less effective. The membrane expression of gp130 was downregulated to 1-2%. IL-6 led to increase of the sIL-6R in the supernatant (P < 0.001) and raised the proliferation of the myeloma cells up to a mean of 124% (P < 0.001). These results indicate that the human myeloma cell line OPM-2 has an autocrine IL-6 regulation mechanism, with an additional paracrine signalling by exogenous IL-6. This is the first report that IL-6 inhibits the membrane expression of gp130, although the proliferation of the myeloma cells increases. VA extract did not affect survival, the expression of surface receptors IL-6 and gp130 or the amount of sIL-6R in the supernatant. However, the proliferation of the tumour cells was inhibited significantly (P < 0.05) suggesting a possible arrest in the cell cycle.     

干扰素α-1b、白介素-2联合沙利度胺方案治疗急性髓系白血病免疫调节作用的协同机制研究

目的:探讨干扰素α-1b、白介素-2联合沙利度胺(简称"干白沙"方案)治疗急性髓系白血病(AML)的免疫调节的协同作用机制.方法:对2016年3月至2019年5月郑州大学附属肿瘤医院等11家医疗单位收治的初治或复发/难治性或行维持治疗的且自愿接受"干白沙"方案治疗的68例AML患者,采集患者用药前1天及规范用药3个月后...     

特发性血小板减少性紫癜患者白细胞介素2及T淋巴细胞研究

应用小鼠脾细胞法及间接免疫荧光法检测了２６例ＩＴＰ患者外周血淋巴细胞产生白细胞介素２（ＩＬ－２）及其受体（ＩＬ－２Ｒ）能力与Ｔ细胞亚群百分率。结果表明，ＩＴＰ患者外周血淋巴细胞产生ＩＬ－２及ＩＬ－２Ｒ的能力低下，Ｔ辅助细胞（ＣＤ＿４￣＋）百分率降低，Ｔ抑制细胞（ＣＤ＿８￣＋）百分率增高（Ｐ＜０．０１）。ＩＬ－２活性与ＣＤ＿４￣＋／ＣＤ＿８￣＋比值呈正相关。１０例ＩＴＰ患者血清可使正常外周血单个核细胞产生ＩＬ－２减少和ＩＬ－２Ｒ表达能力降低。     

Effects of isolated limb perfusion with tumour necrosis factor-alpha on the function of monocytes and T lymphocytes in patients with cancer

The objective of the present study was to investigate the effects of isolated limb perfusion (ILP) with tumour necrosis factor alpha (TNF-α) and melphalan in patients with cancer on, first, plasma levels of cytokines, second, systemic monocyte and T-lymphocyte distribution and, third, the ability of mononuclear cells to produce cytokines upon stimulation in vitro. Six patients undergoing an ILP were entered into the study (group 1). In addition, patients undergoing a major surgical operation (group 2), minor operation (group 3) as well as healthy volunteers (group 4) were included as control groups. Sensitive enzyme-linked immunosorbent assays (ELISAs) were used to measure TNF-α and interleukin-6 (IL-6) plasma levels at various time points during and after operation. Furthermore, the percentage of monocytes and T lymphocytes was determined in all studied groups using a FACScan. In addition, cytokine production upon stimulation with lipopolysaccharide (LPS) and a combination of anti-CD3/anti-CD28 monoclonal antibodies in whole-blood cultures was investigated. Increased plasma levels of TNF-α and IL-6 in patients undergoing ILP was observed, but only IL-6 appeared to be increased in patients treated with a major operation. No significant fluctuations were found in the other groups studied. Concerning the number of monocytes, a significant decrease was observed only in patients treated with ILP. Furthermore, a decreased production of TNF-α, IL-6 and IL-8 upon various types of stimulation in vitro was found in those patients, but also after a major operation. In conclusion, the results of the present study show increased plasma levels of cytokines in patients treated with ILP and major operation. Furthermore, a decrease in numbers of monocytes in the circulation and the ability of mononuclear cells to produce cytokines in vitro may be induced by administration of TNF-α in ILP. Although similar results were found in patients treated with major operation, the underlying mechanisms of this phenomenon remain to be elucidated.     

白细胞介素在扩张型心肌病患者血清中的表达及意义

目的观察扩张型心肌病（DCM）患者血清中的白细胞介素6（IL-6）,白细胞介素1α（IL-1α）,可溶性白细胞介素-2受体（SIL-2R）及白细胞介素10（IL-10）的水平,探讨其意义。方法扩张型心肌病患者组35例,健康对照组21例,用ELISA方法测定IL-6,IL-1α,SIL-2R,IL-10水平,并对其结果进行比较。结果DCM患者血清中IL-6,IL-1α,SIL-2R及IL-10水平明显高于健康对照组（P〈0.05）。结论DCM患者血清中IL-6,IL-1α,sIL-2R及IL-10水平的升高,说明DCM的发生、发展与免疫因素重要相关。