Soluble and Cell-Associated Forms of Some Yet to be Identified Factor in Transfused Blood Which Promotes Solid Tumor Growth in Mice

Purpose The mechanism underlying the immunomodulation caused by blood transfusion has yet to be elucidated. The aim of the present study was to determine whether the transfusion of a soluble or insoluble factor present in stored blood can induce immunomodulation, which would thereby promote solid tumor growth.Methods C57Bl/6J mice were subcutaneously inoculated with B16-CG melanoma cells, which secrete -human chorionic gonadotropin (-hCG). Following inoculation, each of three different products of allogeneic and syngeneic blood were transfused on days 0 and 1: fresh whole blood, stored whole blood, and supernatants from the stored blood. Tumor growth was then monitored by measuring urinary -hCG. All mice were killed on day 15, and the tumor weight and volume were measured.Results Transfusion of all allogeneic blood products enhanced tumor growth, as did the stored syngeneic whole blood. Neither fresh syngeneic blood nor the supernatant from stored syngeneic blood promoted tumor growth. Although the tumors were not visually detectable until day 10 after inoculation, by day 7 the levels of urinary -hCG were significantly higher in the mice that received allogeneic blood supernatant than in the mice that received saline.Conclusions A soluble alloantigen enhances solid tumor growth, as does an insoluble factor present in stored syngeneic whole blood. The immunomodulation associated with this factor begins to enhance tumor growth within 7 days after transfusion.     

Inhibitory effect of a polysaccharide from Tinospora cordifolia on experimental metastasis

Administration of the polysaccharide fraction from Tinospora cordifolia was found to be very effective in reducing the metastatic potential of B16F-10 melanoma cells. There was a 72% inhibition in the metastases formation in the lungs of syngeneic C57BL/6 mice, when the drug was administered simultaneously with tumour challenge. Biochemical parameters such as lung collagen hydroxyproline, hexosamines and uronic acids that are markers of neoplastic development were reduced significantly (P<0.001) in the treated animals compared with the untreated control animals. The treatment could also reduce serum γ-glutamyltranspeptidase (γ-GT) and sialic acid levels as compared to the control animals.     

Comparison of Plasma Levels of Cytokines and In Vitro Generation of Reactive Oxygen Species After Nicotine Infusion in Nicotine Users with Normal and Impaired Renal Function

Several in vitro and animal studies suggest effects of nicotine on the immune system, but little evidence exists regarding the in vivo immunomodulation of nicotine in humans. The increased use of nicotine replacement therapy to aid smoking cessation claims further understanding of how nicotine affects blood leukocytes. This is of particular importance when nicotine therapy is used in diseases associated with alterations of the immune system, such as chronic renal failure. The present study evaluates the acute effects of nicotine infusion (NI) on some immunoregulatory functions in seven healthy subjects and seven patients with renal failure. All subjects were nicotine users and had refrained from using nicotine for 36 h before NI. Blood was collected before, immediately after, and 2 h after NI. Plasma concentrations of intercellular adhesion molecule-1 (ICAM-1) and the cytokines interleukin-2 (IL-2), IL-4, IL-10, interferon-γ and RANTES were measured using specific immunoassays. The generation of reactive oxygen species (ROS) induced by formyl-methionyl-leucyl-phenylalanine (fMLP), Ristocetin, adenosine 5'-diphosphate, or collagen was registered in whole blood as luminol-dependent chemiluminescence. Except for fMLP, these compounds induce leukocyte ROS generation by platelet mediated mechanisms. NI did not significantly affect the levels of the cytokines and ICAM-1 in any group. The peak and the persistent ROS production, induced by collagen and Ristocetin, was lower at some time points in patients with renal failure as compared to healthy subjects. Also in patients with renal failure, both peak height and persistent ROS generation induced by Ristocetin were reduced immediately after NI. Thus, nicotine inhibits some of the platelet-mediated activation of leukocyte ROS generation, and may be associated with platelet defects in renal failure.     

Supplementation with aqueous leaf extract of Morinda lucida enhances immunorestoration and upregulates the expression of cytokines and immunostimulatory markers

Morinda lucida Benth (Rubiaceae) is a versatile plant used in traditional medicine of many countries for the treatment of a variety of ailments and the claims of efficacy are particularly remarkable in the treatment of infections and immuno-inflammatory disorders. In this study, we investigated the immunostimulatory and immunorestorative properties of the aqueous leaf extract of Morinda lucida (AML) in cultures of murine splenic lymphocytes and in cyclophosphamide-induced immunosupression models, respectively. Administration of AML (100 and 250 mg/kg; per os) in alternate days significantly (P < 0.05) increased specific total IgG, IgG1, and IgG2a responses to ovalbumin by as much as 2-10 fold when compared to untreated controls. In cyclophophamide treated mice, the rate of wound healing, leukopoiesis , and body weight recovery were all enhanced by oral supplementation with AML (100 and 250 mg/kg) in a dose-dependent manner. In vitro cultures of BALB/C splenocytes treated with AML (12.5 and 50 μg/ml) for 24 h resulted in 5-10 fold increase in IFNγ and IL-4 measured by cytokine capture ELISA. Surface expression of immunostimulatory markers, CD69 and CD25, measured flow cytometrically by FACS analyis, were also significantly (P < 0.05) upregulated on splenic T and B cells by as much as 8-20 fold. Taken together, the results of these studies show the potent immunostimulatory and immunorestorative properties of the aqueous leaf extract of Morinda lucida, which may explain some of the beneficial effects of the plant in the treatment of infections and immuno-inflammatory disorders.     

Administration of Thymopentin to Patients with Phobic Disorders Improves Depressed Phagocytic Functions

Seven patients with phobic disorders were administg red with a synthetic thymic extract, thymopentin (TP-S), in order to correct depressed polymorphonuclear cell (PMN) and monocyte phagocytosis and killing capacities. Subcutaneous administration (50 mg, three times weekly, for a period of 8 wks) of TP-5 resulted in a significant increase in phagocytic function with no change in the phagocytic capacity of PMN. These data support the concept that immunomodulators can achieve a correction of immune deficiencies associated with phobic disorders.     

Immunomodulatory effects of deferoxamine and interferon gamma on human dental pulp stem cells北大核心

BACKGROUND: Immune rejection is a great challenge for tissue or organ transplantation, and immunosuppressors often bring serious side effects to patients. The immunosuppressive effect of mesenchymal stem cells brings new hope for the treatment of immune rejection. OBJECTIVE: To explore the effect of combined action of deferoxamine and interferon-γ on the immunomodulatory ability of human dental pulp stem cells. METHODS: After pretreatment of human dental pulp stem cells with deferoxamine or interferon-γ or their combination, the proliferation of cells was detected with cell counting kit-8. The mRNA expression of some gene mRNA was examined by Q-PCR. The secretion of some immune regulatory factors was determined using ELISA. Thereafter, pretreated human dental pulp stem cells were co-cultured with mouse spleen lymphocytes, and then the proliferation of lymphocytes was detected by CFSE labeling by flow cytometry. After allogenic skin transplantation, mice were injected with PBS, human dental pulp stem cells or pretreated human dental pulp stem cells into tail vein immediately. The survival time of skin grafts was recorded. The pathology and immunohistochemistry of skin grafts were examined. Moreover, the proportion of Treg cells in spleen of transplanted mice was measured. RESULTS AND CONCLUSION: (1) Deferoxamine or interferon-γ pretreatment inhibited the growth of human dental pulp stem cells, and the inhibition of deferoxamine was more significant than interferon-γ. (2) Pretreatment of deferoxamine combined with interferon-γ significantly increased the gene expression of vascular endothelial growth factor, interleukin 6, transforming growth factor β1, cyclooxygenase 2, human leukocyte antigen G, tumor necrosis factor A inducible protein 6 and interleukin 10, and promote secretion of interleukin 6, transforming growth factor β1 and prostaglandin E2. (3) The results of in vivo experiments confirmed that human dental pulp stem cells pretreated with deferoxamine combined with interferon-γ prolonged the survival time of mouse allograft skin, reduced the infiltration of CD4+T, CD8+T and macrophages at the grafted skin, and increased the proportion of Treg cells in the spleen of recipient mice. (4) It is concluded that deferoxamine combined with interferon-γ pretreatment enhanced the immunomodulatory effect of human dental pulp stem cells, and inhibited the immune rejection of skin allografts. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

间充质干细胞通过调控巨噬细胞极化实现免疫应答的研究现状

间充质干细胞(MSC)是一种具有自我更新及多向分化潜能的多能干细胞,是细胞移植治疗的研究热点。既往认为,MSC主要通过细胞替代达到治疗疾病的目的。近年多项研究结果表明,MSC在调控免疫应答、抑制炎症反应中,也具有重要作用。新生儿缺血缺氧性脑病(HIE)是引起新生儿死亡和伤残的重要原因。对HIE采取MSC移植治疗,可减轻缺血缺氧引起的炎症损伤,加速神经修复。然而,MSC的免疫调控作用并不是与生俱来的,而与局部炎症微环境密切相关,在不同水平炎症因子的刺激下,MSC可表现出截然不同的免疫作用。深入探讨MSC的免疫调控机制,有助于进一步对其临床应用进行研究。笔者拟就炎症微环境刺激下,MSC的免疫调控作用及其机制进行阐述。     

Adhesion and immunomodulatory effects of Bifidobacterium lactis HN019 on intestinal epithelial cells INT-407

AIM:To elucidate the adherence and immunomodulatory properties of a probiotic strain Bifidobacterium lactis(B.lactis) HN019.METHODS:Adhesion assays of B.lactis HN019 and Salmonella typhimurium(S.typhimurium) ATCC 14028 to INT-407 cells were carried out by detecting copies of species-specific genes with real-time polymerase chain reaction.Morphological study was further conducted by transmission electron microscopy.Interleukin-1β(IL-1β),interleukin-8,and tumor necrosis factor-α(TNF-α) gene expression were as...     

Toxicological and immunomodulatory assessments of botryosphaeran (β-glucan) produced by Botryosphaeria rhodina RCYU 30101

Toxicological and immunomodulatory activities of botryosphaeran (BR), a newly emerged β-glucan that comprises a β-(1→3) backbone and β-(1→6) branched glucose residues were assessed. BR was 1.82 × 10⁶ Da (M.W.) estimated by reversely-linear equation constructed by regression of logarithms of standard polysaccharides and their retention times of gel permeation chromatography. Sprague-Dawley rats were daily gavage-administered with BR at doses of 0, 1.25, 12.5, and 125 mg/kg body weight (BW) for 28 d. Serum hematological and biochemical analysis of all treatment were all within normal ranges. Mitogen-stimulated lymphoblastogenesis of spleno-lymphocytes was enhanced by BR at doses of 1.25 and 12.5 mg/kg BW. Through in vitro comparative assessments, RAW 264.7 macrophage (RAW) cells were treated with BR and two commercial β-glucans, zymosan (ZY) and barley β-glucan (GB), to characterize their relative immunomodulatory properties. All three β-glucans stimulated phagocytosis on fluorescence-labeled Escherichia coli. At dose levels from 5 to 200 μg/mL for 24 h, nitric oxide produced by BR- and ZY-treated cells were higher than those produced by GB-treated and control groups. BR, ZY but GB also stimulated RAW cells in producing TNF-α. The results demonstrate that BR is toxicologically accepted and features as a potent immunomodulator.