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T cell growth factor [keywords]
- [Clinical efficacy of adjuvant therapy with glucocorticoids in children with lobar pneumonia caused by Mycoplasma pneumoniae]. [English Abstract, Journal Article]
- Zhongguo Dang Dai Er Ke Za Zhi 2014 Apr; 16(4):401-5.
To study the clinical efficacy of adjuvant therapy with glucocorticoids in children with lobar pneumonia caused by Mycoplasma pneumoniae.One hundred and eight children with lobar pneumonia caused by Mycoplasma pneumoniae were randomly divided into routine treatment and hormone treatment groups. Both groups were treated with azithromycin and other symptomatic therapies. In addition to the basic treatment, the hormone treatment group was given dexamethasone 0.25-0.3 mg/(kg·d) by intravenous drip until the body temperature was normal. Then given oral prednisone tablets 0.5-1 mg/(kg·d) (gradually reduced) for a total treatment course of 7-10 days. Before and after treatment pulmonary functions were examined, and serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-2 (IL-2) and interleukin-6 (IL-6) were measured.The duration of fever, cough relief time and pulmonary shadow absorption time on chest X-ray were significantly shorter in the hormone treatment group than in the routine treatment group (P<0.05). After treatment, the two groups showed improvements in serum CRP, ESR, IL-2, and IL-6 (P<0.05), but the hormone treatment group showed significantly more improvement (P<0.05). Varying degrees of mixed ventilation dysfunction were seen in the two groups before treatment, and hormone therapy significantly improved pulmonary function, especially promoting the recovery of small airway function.Adjuvant therapy with glucocorticoids can effectively alleviate clinical symptoms, promote the absorption of pulmonary inflammation, and improve pulmonary function in children with lobar pneumonia caused by Mycoplasma pneumoniae.
- Post-traumatic Immunosuppression is Reversed by Anti-coagulated Salvaged Blood Transfusion; Deductions from studying Immune Status after Knee Arthroplasty. [JOURNAL ARTICLE]
- Clin Exp Immunol 2014 Apr 18.
Major trauma increases vulnerability to systemic infections due to poorly defined immunosuppressive mechanisms. It confers no evolutionary advantage. Our objective was to develop better biomarkers of post-traumatic immunosuppression (PTI); and to extend our observation that PTI was reversed by anti-coagulated salvaged blood transfusion, in the knowledge that others had shown that non-anti-coagulated (fibrinolysed) salvaged blood was immunosuppressive. A prospective non-randomized cohort study of patients undergoing primary total knee arthroplasty included 25 who received salvaged blood transfusions collected post-operatively into Acid-Citrate-Dextrose anti-coagulant (ASBT cohort), and 18 non-transfused patients (NSBT cohort). Biomarkers of sterile trauma included haematological values, Damage-Associated-Molecular-Patterns (DAMPs), cytokines, and chemokines. Salvaged blood was analysed within one hour and six hours after commencing collection. Biomarkers were expressed as fold-changes over pre-operative values. Certain biomarkers of sterile trauma were common to all 43 patients, including supra-normal levels of: Interleukin-6, Interleukin-1-Receptor-Antagonist, Interleukin-8, Heat-Shock-Protein-70, and Calgranulin-S100-A8/9. Other pro-inflammatory biomarkers which were subnormal in NSBT became supra-normal in ASBT patients, including: Interleukin-1-beta, Interleukin-2, Interleukin-17A, Interferon-gamma, Tumour-Necrosis-Factor-alpha, and Annexin-A2. Furthermore, ASBT exhibited sub-normal levels of anti-inflammatory biomarkers: Interleukin-4, Interleukin-5, Interleukin-10, and Interleukin-13. Salvaged blood analyses revealed sustained high levels of, Interleukin-9, Interleukin-10, and certain DAMPs including: Calgranulin-S100-A8/9, alpha-Defensin, Heat-Shock-Proteins-27, 60, and 70. Active synthesis during salvaged blood collection yielded increasingly elevated levels of: Annexin-A2, Interleukin-1-beta, Interleukin-1-Receptor-Antagonist, Interleukin-2, Interleukin-4, Interleukin-6, Interleukin-8, Interleukin-10, Interleukin-12p70, Interleukin-17A, Interferon-gamma, Tumor-Necrosis-Factor-alpha, Transforming-Growth-Factor-Beta-1, Monocyte-Chemotactic-Protein-1, and Macrophage-Inflammatory-Protein-1-alpha. Elevated levels of High-Mobility-Group-Box-Protein-1 decreased. In conclusion, we demonstrated that anti-coagulated salvaged blood reversed PTI, and was attributed to immune stimulants generated during salvaged blood collection.
- Effect of heavy-ion beam irradiation on the level of serum soluble interleukin-2 receptors in hamster cheek pouch carcinoma model. [JOURNAL ARTICLE]
- Biomed Rep 2014 May; 2(3):408-411.
Soluble interleukin-2 receptor (sIL-2R) is a glycoprotein derived from α chain of interleukin 2 receptors of mononuclear as well as T-cell membranes. The aims of this study were to detect the changes of serum soluble interleukin-2 receptor (sIL-2R) levels following heavy-ion beam irradiation in the hamster model with cheek pouch carcinoma, as well as to examine the impact of immune status of the hamster cheek pouch carcinoma model using heavy-ion beam irradiation. sIL-2R serum levels were detected by radioimmunoassay (RIA) in 40 hamsters bearing cheek pouch carcinoma prior to and following exposure to heavy-ion beam irradiation, and 8 normal animals served as the control. The sIL-2R serum level in hamster cheek pouch carcinoma model was significantly increased as compared to the normal control group (P<0.05). Results showed that an increase in the irradiation dose led to a gradual decrease in the sIL-2R serum level. Additionally, a statistical significance was observed compared to the tumor group (P<0.05). In conclusion, alterations in serum sIL-2R expression have an effect on the hamsters cheek pouch carcinoma model subsequent to heavy-ion beam irradiation. An increase in the irradiation dose indicated a decreased tendency in serum sIL-2R content. Detection of serum level changes may lead to an improved understanding of heavy-ion irradiation in vivo immune status, which is crucial for clinical diagnosis and prognosis. It can also provide a sensitive indicator to help estimate the effects of heavy-ion cancer targets.
- Current strategies for immunosuppression following liver transplantation. [JOURNAL ARTICLE]
- Langenbecks Arch Surg 2014 Apr 20.
New strategies for immunosuppression (IS) after liver transplantation (LTx) are in part responsible for the increased patient and graft survival seen over time. With a few basic exceptions-notably the continued use of steroids and calcineurin inhibitors (CNIs)-IS drugs and regimens being used today are different from those used 30 years ago. While graft loss due to acute or chronic rejection has become rare, the side effect burden of IS drugs exerts a significant toll on patients.CNIs continue to form the backbone of IS regimens, although their use is hampered by nephrotoxicity and other adverse effects. Consequently, a variety of CNI reduction or withdrawal strategies have formed the basis of clinical trials or entered into clinical practice. These trials have included the use of everolimus, an mTOR inhibitor, and anti-interleukin-2 receptor antibodies. Basiliximab, as well as other lymphocyte nondepleting and depleting agents, have shown benefit in induction regimens. Along with steroid reduction or elimination, current strategies for IS after LTx continue to explore novel combinations of agents, with an aim toward striking a balance between diminution of rejection and the need for avoiding adverse effects of the IS drugs. Long-term maintenance strategies are also discussed in this review, as is development of tolerance and antibody-mediated rejection.
- A case of thyroid storm with a markedly elevated level of circulating soluble interleukin-2 receptor complicated by multiple organ failure and disseminated intravascular coagulation syndrome. [JOURNAL ARTICLE]
- Endocr J 2014 Apr 20.
Thyroid storm (TS) is a life-threatening endocrine emergency. However, the pathogenesis of TS is poorly understood. A 40-year-old man was admitted to a nearby hospital with body weight loss and jaundice. Five days after a contrasted abdominal computerized tomography (CT) scan, he exhibited high fever and disturbance of consciousness. He was diagnosed with TS originating from untreated Graves' disease and was transferred to the intensive care unit (ICU) of our hospital. The patient exhibited impaired consciousness (E4V1M4 in Glasgow coma scale), high fever (39.3°C), and atrial flutter with a pulse rate 162/min, and was complicated by heart failure, acute hepatic failure, and disseminated intravascular coagulation syndrome (DIC). His circulating level of soluble interleukin-2 receptor (sIL-2R), a serum marker of an activated immune response, was highly elevated (7,416 U/mL, reference range: 135-483). Multiple organ failure (MOF) and DIC were successfully managed by multimodality treatments using inorganized iodide, glucocorticoids, anti-thyroid drugs, beta-blockers, and diuretics as well as an anticoagulant agent and the transfusion of platelet concentrate and fresh frozen plasma. sIL-2R levels gradually decreased during the initial treatment, but were still above the reference range even after thyroidectomy. Mild elevations in serum levels of sIL-2R have previously been correlated with thyroid hormone levels in non-storm Graves' disease. The present study demonstrated, for the first time, that circulating sIL-2R levels could be markedly elevated in TS. The marked increase in sIL-2R levels was speculated to represent an inappropriate generalized immune response that plays an unknown role in the pathogenesis of TS.
- Transforming growth factor beta (TGFβ) plays a crucial role in prolonging allograft survival in an allodepletion ("pruning") skin transplant model. [JOURNAL ARTICLE]
- Transpl Immunol 2014 Apr 15.
Adoptive cell therapies, involving cell, manipulation to achieve tolerance are increasingly being studied in animal models and in human trials. We have demonstrated that the specific removal of allo-stimulated dividing cells (or "pruning") promotes long-term allograft survival across a major MHC mismatch in transplant models including skin, heart and islet transplants. In this study, we examine the role of transforming growth factor beta (TGFβ), an important regulatory cytokine, on allograft survival in our allodepletion or "pruning" skin transplant model. Increased proliferation of CD4(+) T cells was observed following allo-stimulation of BALB/c spleen cells (labeled with CFSE) in the presence of the regulatory cytokines TGFβ and (interleukin-2) IL-2 in a mixed lymphocyte culture (MLC). Expression of the regulatory gene forkhead box-3 (FoxP3) was increased in both the allo-stimulated non-dividing (ND) (CFSE(high)) and dividing (D) (CFSE(low)) CD4(+) T cell populations, with the highest expression found in the D CD4(+) T cell population. Mice reconstituted with allo-stimulated ND CD4(+) T cells following TGFβ/IL-2 stimulation showed prolonged allograft survival, similar to previous data. Significantly, TGFβ/IL-2 stimulation prevented acute rejection of allografts across a major MHC mismatch in the presence of highly activated allo-stimulated D CD4(+) T cells. Blockade of TGFβ promoted rejection of allografts even following depletion of allo-stimulated D CD4(+) T cells. These studies support a crucial role for TGFβ in the survival of allografts and shows that regulatory cytokines TGFβ/IL2 can delay the rejection of allografts, even in the presence of highly activated alloreactive T cells.
- Phase I trial of biochemotherapy with cisplatin, temozolomide, and dose escalation of nab-paclitaxel combined with interleukin-2 and interferon-α in patients with metastatic melanoma. [JOURNAL ARTICLE]
- Melanoma Res 2014 Apr 16.
The primary objective of this study was to determine the safety, toxicity, and maximum tolerated dose of nanoparticle albumin-bound (nab)-paclitaxel as part of biochemotherapy for metastatic melanoma and to determine whether substituting nab-paclitaxel for less potent agents could increase response rates and duration. Treatment consisted of intravenous cisplatin (20 mg/m) on days 1-4, oral temozolomide (250 mg/m) on days 1-3, subcutaneous interferon-α (5×10 IU/m) on days 1-5, and continuous intravenous interleukin-2 (9×10 IU/m) for 96 h on days 1-4. A standard 3+3 dose escalation method was used; the nab-paclitaxel starting dose was 100 mg/m on day 1 and 70 mg/m on day 5. The treatment cycle was repeated every 3 weeks and toxicity was assessed weekly. Ten patients were enrolled. Dose-limiting toxicities included diarrhea, transaminasemia, and neutropenia. The maximum tolerated dose was not identified because the nab-paclitaxel dose on day 1 at the lowest planned dose (80 mg/m) caused dose-limiting toxicity in two of five patients. Of the nine patients who were evaluable for response, five had a partial response. The median time to disease progression was 5.30 months and the median overall survival was 8.73 months. Six patients developed central nervous system metastasis at a median of 5.33 months after treatment initiation. Biochemotherapy including nab-paclitaxel according to the doses and schedule regimen used in the present study has significant toxicity. Substituting dacarbazine with temozolomide did not prevent central nervous system metastasis in patients with metastatic melanoma.
- In vivo and in vitro evidence that (99m)Tc-HYNIC-interleukin-2 is able to detect T lymphocytes in vulnerable atherosclerotic plaques of the carotid artery. [JOURNAL ARTICLE]
- Eur J Nucl Med Mol Imaging 2014 Apr 16.
Recent advances in basic science have established that inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Inflammatory cells are thought to be responsible for the transformation of a stable plaque into a vulnerable one. Lymphocytes constitute at least 20 % of infiltrating cells in these vulnerable plaques. Therefore, the interleukin-2 (IL-2) receptor, being overexpressed on activated T lymphocytes, may represent an attractive biomarker for plaque vulnerability. The aim of this study was to evaluate the specificity of radiolabelled IL-2 [(99m)Tc-hydrazinonicotinamide (HYNIC)-IL-2] for imaging the lymphocytic infiltration in carotid plaques in vivo by planar and single photon emission computed tomography (SPECT)/CT imaging and ex vivo by microSPECT and autoradiography.For the in vivo study, ten symptomatic patients with advanced plaques at ultrasound who were scheduled for carotid endarterectomy underwent (99m)Tc-HYNIC-IL-2 scintigraphy. The images were analysed visually on planar and SPECT images and semi-quantitatively on SPECT images by calculating target to background (T/B) ratios. After endarterectomy, immunomorphological evaluation and immunophenotyping were performed on plaque slices. For the ex vivo studies, four additional patients were included and, after in vitro incubation of removed plaques with (99m)Tc-HYNIC-IL-2, autoradiography was performed and microSPECT images were acquired.Visual analysis defined clear (99m)Tc-HYNIC-IL-2 uptake in seven of the ten symptomatic plaques. SPECT/CT allowed visualization in eight of ten. A significant correlation was found between the number of CD25+ lymphocytes and the total number of CD25+ cells in the plaque and the T/B ratio with adjacent carotid artery as background (Pearson's r = 0.89, p = 0.003 and r = 0.87, p = 0.005, respectively). MicroSPECT imaging showed clear (99m)Tc-HYNIC-IL-2 uptake within the plaque wall and not in the lipidic core. With autoradiography, only CD3+ lymphocytes were found to be labelled.These in vivo and ex vivo studies confirm the specificity of (99m)Tc-HYNIC-IL-2 for imaging activated T lymphocytes in carotid plaques. (99m)Tc-HYNIC-IL-2 is a true marker for the inflamed plaque and therefore of plaque instability.
- Pulmonary Toxicity in Mice Following Exposure to Cerium Chloride. [JOURNAL ARTICLE]
- Biol Trace Elem Res 2014 Apr 16.
The widespread application of lanthanoids (Lns) in manufacturing industries has raised occupational and environmental health concerns about the possible increased health risks to humans exposed to Lns in their working and living environments. Numerous studies have shown that exposures to Ln cause pulmonary injury in animals, but very little is known about the molecular mechanisms of the pulmonary inflammation caused by cerium chloride (CeCl3) exposure. In this study, we evaluated the oxidative stress and molecular mechanism underlying with the pulmonary inflammation associated with chronic lung toxicity in mice treated with nasally instilled CeCl3 for 90 consecutive days. Our findings suggest that significant cerium accumulated in the lung, leading the obvious increase of the lung indices, significant increases in inflammatory cells and levels of lactate dehydrogenase, alkaline phosphate, and total protein, overproduction of reactive oxygen species and peroxidation of lipids, reduced antioxidant capacity, and pulmonary inflammation. CeCl3 exposure also activated nuclear factor κB, increased the expression of tumor necrosis factor α, cyclooxygenase-2, heme oxygenase 1, interleukin 2, interleukin 4, interleukin 6, interleukin 8, interleukin 10, interleukin 18, interleukin 1β, and CYP1A1. However, CeCl3 reduced the expression of nuclear factor κB (NF-κB)-inhibiting factor and heat shock protein 70. These findings suggest that the pulmonary inflammation caused by CeCl3 in mice is closely associated with oxidative stress and inflammatory cytokine expression.
- Successes and limitations of targeted therapies in renal cell carcinoma. [Journal Article]
- Prog Tumor Res 2014.:98-112.
Until recently, the standard treatment for metastatic renal cell carcinoma (RCC) was nonspecific immunotherapy based on interleukin-2 or interferon-α. This was associated with a modest survival benefit and with significant clinical toxicities. The understanding of numerous molecular pathways in RCC, including HIF, VEGF, mTOR, and the consecutive use of targeted therapies since the beginning of 2005 have significantly improved outcomes for patients with metastatic RCC with an overall survival greater than 2 years. At present, at least 7 targeted agents are approved for first and consecutive lines of treatment of clear cell metastatic RCC. Long-term benefit and extended survival may be achieved through the optimal use of targeted therapies: optimal dosing, adverse event management and treatment duration and compliance. Advances in the finding of prognostic factors highlight the potential for personalizing treatment for patients with metastatic RCC. Data regarding the best sequencing of targeted therapies, predictive biomarkers, best timing of surgery, patient risk profiles, understanding of resistance mechanisms and safety of targeted therapies are growing and will provide a further step ahead in the management of advanced RCC. In parallel, a new class of therapeutics is emerging in RCC: immunotherapy; in particular check-point blockade antibodies are showing very promising results. © 2014 S. Karger AG, Basel.