OBJECTIVETo study the efficacy and safety of Shuanghuang Shengbai Granule (, SSG), a traditional Chinese herbal medicine, on myelosuppression of cancer patients caused by chemotherapy.

METHODSA total of 330 patients were randomly assigned to the treatment group (220 cases, analysed 209 cases) and the control group (110 cases, analysed 102 cases) with a 2:1 ratio by envelope method. The patients in the treatment group at the first day of chemotherapy started to take SSG for 14 days, while the patients in the control group took Leucogon Tablets. The changes of the blood routine, clinical symptoms and immune function in both groups were observed for safety and efficacy evaluation.

RESULTSAt the 7th day of chemotherapy, the white blood cells (WBCs) level in the treatment group was significantly higher than that in the control group (P<0.05). After treatment, the WBCs rate in the normal range accounted for 50.2% in the treatment group, the myelosuppression of WBCs and neutrophil were mainly grade I, while 8.1% and 5.7% of patients emerged grade III and grade IV myelosuppression, respectively. The incidence of myelosuppression of the treatment group was significantly lower than that of the control group (P<0.05). The total effective rate of Chinese medicine syndrome in the treatment group was significantly higher than that in the control group (84.2% vs. 72.5%, P<0.05). The immune cell levels in both groups were maintained in the normal range. Compared with that before treatment, the levels of CD3and CD4cells were significantly increased in the treatment group after treatment (P<0.05). The discrepancy of CD3and CD4cell activity before and after treatment in both groups were significantly different (P<0.05). No obvious adverse event occurred in both groups.

CONCLUSIONSSG had a protection effect on bone marrow suppression, and alleviated the clinical symptoms together with clinical safety.

Antineoplastic Agents, Phytogenic ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Granulocyte Precursor Cells ; drug effects ; Humans ; Immune Tolerance ; drug effects ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Neoplasms ; drug therapy ; Pancytopenia ; chemically induced ; prevention & control ; Treatment Outcome

Asian Continental Ancestry Group ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Immune Tolerance ; drug effects ; Materia Medica ; therapeutic use ; Medicine, Chinese Traditional ; Pregnancy ; Pregnancy Complications ; drug therapy

OBJECTIVETo test the effect of bifunctional molecule IL2-GMCSF in promoting the activation of dendritic cells (DCs) cultured in tumor conditioned medium.

METHODSWe prepared a tumor conditioned medium using mouse melanoma cell line B16F10 supplemented with IL2-GMCSF, GM-CSF, IL-2, or the combination of the latter two. After culturing mouse DC cell line DC2.4 in the conditioned medium for 24 h, the DCs were examined for phagocytosis, proliferation, maturation phenotype, cytokine secretion, and signal pathway activation.

RESULTSDC2.4 cells displayed characteristics of immature DCs. After cell culture in the conditioned medium, the cells showed enhanced phagocytosis but significantly suppressed cell proliferation activity. Culture in the conditioned medium also promoted DC cell maturation and secretion of macrophage-derived chemokine (MDC), but inhibited IL-12 secretion. Supplementation of the conditioned medium with IL2-GMCSF promoted phagocytosis, proliferation, maturation, and cytokine (including both IL-12 and MDC) secretion of DC2.4 cells. Compared with GM-CSF, IL2-GMCSF induced a higher level of NF-κB signal pathway activation but suppressed STAT3 activation.

CONCLUSIONCompared with GM-CSF, IL2-GMCSF can better promote DC activation in the context of tumor-induced immune suppression, and thus shows potentials in anti-tumor therapy.

Animals ; Cell Differentiation ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Chemokine CCL22 ; metabolism ; Culture Media, Conditioned ; chemistry ; Dendritic Cells ; cytology ; drug effects ; Gene Expression Regulation, Neoplastic ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Immune Tolerance ; Interleukin-12 ; metabolism ; Interleukin-2 ; pharmacology ; Melanoma, Experimental ; pathology ; Mice ; NF-kappa B ; metabolism ; Phagocytosis ; STAT3 Transcription Factor ; metabolism ; Signal Transduction

OBJECTIVETo explore the biological characteristics and the immuno-suppression function of tolerogenic dendritic cells (tDC) induced by tacrolimus.

METHODSHuman monocytes derived from peripheral blood were cultured in the cGMP-compliant CellGro DC medium supplemented with GM-CSF and IL-4 to obtain dendritic cells (DCs), and 0.1 μmol/L immunosuppressive drug tacrolimus was added to the culture medium at the third and fifth day to obtain tDCs. The molecular markers of them and the livability were assayed by flow cytometry. Then the tolerance functionality of tDCs induced by many agents and these tDCs modulated allogeneic CD4 T cells was determined via CFSE proliferation assay. And the research also analyzed the biological characters and immunosuppression function of tDCs induced by tacrolimus after storing.

RESULTStDCs induced by tacrolimus exhibit a typical tolerogenic phenotype, whose level of costimulatory molecules CD80, CD83, CD86 and HLA-DR is (2.95 ± 1.32)%, (2.33 ± 1.60)%, (90.02 ± 7.42)% and (91.80 ± 6.18)%, respectively. It's survival rate was (85.2 ± 4.72)%. And immunosuppressive drugs didn't influence the differentiation of tDCs from monocytes. tDCs induced by immunosuppressive drugs dexamethasone, cyclosporin A and tacrolimus had lower immunogenic than control DCs as CD4+ T proliferation rate of tDCs induced by tacrolimus is 0.42% and could not primed allogeneic CD4+ T cells proliferation. Functional analyses showed that tDCs induced by tacrolimus can more effectively suppressed mature DC-induced T cell proliferation than other tDCs, whose inhibition rate can reach (67.01 ± 19.73)%. Importantly, tDCs induced by tacrolimus had phenotypical and functional stability after storing.

CONCLUSIONtDCs induced by tacrolimus with tolerance functionality are a promising cellular therapeutic for immunomodulation.

Cell Proliferation ; drug effects ; Cells, Cultured ; Dendritic Cells ; drug effects ; immunology ; Humans ; Immune Tolerance ; drug effects ; Lymphocyte Culture Test, Mixed ; Tacrolimus ; pharmacology

OBJECTIVEThe incidence of food allergy has increased in recent years and there is no effective way to treat it except strict dietary avoidance and rapid medical treatment in case of accidental exposure. Oral tolerance, as a new method, has shown great promise as an alternative approach to prevention and treatment for allergic disease. It was reported that all-trans retinoic acid (atRA) plays an important role in inducing oral tolerance in vitro. Our study aimed to investigate the immunological effect of different doses of atRA on ovalbumin (OVA) allergic BALB/c mice.

METHODBALB/c mice were sensitized by intraperitoneal injection with OVA to establish allergic animal model. According to the dose of atRA given, 40 OVA allergic BALB/c mice were divided into 4 groups: the mice in high dose group were treated with 100 mg/kg atRA (atRA-H), those in median dose group were treated with 50 mg/kg atRA (atRA-M), those in low dose group were treated with 20 mg/kg atRA (atRA-L) and the mice in control group were given vehicle-soy oil only (CTR). After 12 days of atRA intervention, weight was measured, the mice were checked for diarrhea , and intestinal histology was observed after hematoxylin and eosin staining. The level of OVA-IgE in serum, total IgA and OVA-IgA in feces were measured by ELISA. The percentage of CD4⁺ CD25⁺ FoxP3⁺ T cells in CD4⁺ T cells in mesenteric lymph node was detected by flow cytometry.

RESULTCompared with that of CTR group, the level of OVA-IgE in serum (1.221 ± 0.367 vs. 0.793 ± 0.616) and OVA-IgA (1.573 ± 0.656 vs. 0.905 ± 0.279) in feces decreased significantly (P = 0.006 and 0.012, respectively) without weight and intestinal histology changes after low dose of atRA administration. However, there was no significant difference in the percentage of CD4⁺ CD25⁺ FoxP3⁺ T cells in CD4⁺ T cells in mesenteric lymph node (10.641 ± 1.218 vs. 10.936 ± 0.954) between atRA-L and CTR group (P > 0.05). While in animals with high and median dose of atRA administration, no immunologic improvement was found, instead, there was weight loss and intestinal mucosal damage.

CONCLUSIONLow dose of atRA intervention seems to induce immune suppression in vivo resulting in positive effects on OVA allergic mice. However, median and high dose atRA had no therapeutic effect on OVA allergic mice.

Animals ; CD4-Positive T-Lymphocytes ; Food Hypersensitivity ; drug therapy ; immunology ; Immune Tolerance ; drug effects ; Lymph Nodes ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; immunology ; T-Lymphocytes, Regulatory ; Tretinoin ; administration & dosage ; pharmacology

Blood Coagulation Factor Inhibitors ; antagonists & inhibitors ; blood ; Factor VIII ; administration & dosage ; antagonists & inhibitors ; immunology ; Hemophilia A ; drug therapy ; genetics ; immunology ; Humans ; Immune Tolerance ; Isoantibodies ; blood ; immunology ; Recombinant Proteins ; adverse effects ; immunology ; therapeutic use ; Risk Factors ; Time Factors

The purpose of this study was to evaluate the effect of meloxicam (MEL) on selected immune parameters of bovine CD25highCD4+, CD25lowCD4+, and CD25-CD4+ cells. Peripheral blood mononuclear cells (PBMCs) collected from 12-month-old heifers were treated with MEL at a concentration corresponding to the serum level of this medication following administration at the recommended dose (MEL 5 x 10(-6) M) and at a concentration 10 times lower (MEL 5 x 10(-7) M). After 12 and 24 h of incubation with the drug, the percentage of CD25highCD4+ cells decreased; however, this disturbance was quickly reversed. Furthermore, the absolute number of CD25highCD4+ cells in the PBMC populations treated with MEL 5 x 10(-6) M for 48 and 168 h was increased. Prolonged (168 h) exposure to the drug increased the percentage of Foxp3+ cells in the CD25highCD4+ cell subpopulation. The higher dose of MEL was found to significantly increase the percentage of IFN-gamma+ cells among the CD25-CD4+ cells. These results indicated that MEL does not exert an immunosuppressive effect by depleting CD4+ cells and suppression of IFN-gamma+ production by these cells. Furthermore, IL-10 and TGF-beta production was not changed following exposure to MEL.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage/*pharmacology ; Apoptosis/*drug effects ; CD4-Positive T-Lymphocytes/*drug effects/metabolism ; Cattle ; Cytokines/metabolism ; Dose-Response Relationship, Drug ; Female ; Forkhead Transcription Factors/*genetics/metabolism ; Gene Expression Regulation/*drug effects ; Immune Tolerance/drug effects ; Interleukin-2 Receptor alpha Subunit/*metabolism ; Leukocytes, Mononuclear/drug effects/metabolism ; Thiazines/administration & dosage/*pharmacology ; Thiazoles/administration & dosage/*pharmacology

OBJECTIVETo compare the effects of Bushen Jiedu Recipe (BJR) and Jianpi Jiedu Recipe (JJR) containing plasma on dendritic cells (DCs) of chronic hepatitis B virus (HBV) infection patients under different immune states.

METHODSRecruited were 36 chronic HBV infection outpatients from First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from April 2010 to January 2011. They were assigned to the immune tolerance group (18 cases) and the immune clearance group (18 cases).Another 10 healthy subjects were recruited as the healthy control group. Their anticoagulated peripheral venous blood was respectively collected. The peripheral blood mononuclear cells (PBMCs) were isolated and further extracted for incubating DCs. The DCs were intervened by BJR and JJR containing plasma. The morphology of DCs was identified. The expressions of CD1alpha, CD80, CD86, and HLA-DR were detected. The level of interferon-alpha (IFN-alpha) in the supernatant was observed by ELISA.

RESULTSThe CD80 expression level was lower in the immune clear group than in the healthy control group before intervention (P < 0.05). The expression levels of CD80, CD86, and HLA-DR were lower in the immune tolerance group than in the healthy control group before intervention (P < 0.05).The IFN-alpha expression level was lower in the immune tolerance group and the immune clearance group than in the healthy control group before intervention (P < 0.05). The expression levels of CD80, HLA-DR, and IFN-alpha were lower in the immune tolerance group than in the immune clearance group before intervention (P < 0.05). Compared with the same group before intervention, the CD80 expression significantly increased in each treatment group (P < 0.05). After intervention the expression levels of CD80 and HLA-DR were higher in the immune tolerance group than in the immune clearance group in the same time phase, and the CD86 expression level was higher in the BJR group than in the immune clearance group in the same time phase, showing statistical difference (P < 0.05).

CONCLUSIONSThe middle dose BJR and the small dose JJR both could promote the recovery of DCs in chronic HBV infection patients. Besides, BJR showed more prominent effects on the function of DCs in chronic HBV infection patients in the immune tolerance stage.

Adult ; B7-1 Antigen ; metabolism ; B7-2 Antigen ; metabolism ; Case-Control Studies ; Dendritic Cells ; drug effects ; immunology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; HLA-DR Antigens ; metabolism ; Hepatitis B, Chronic ; blood ; drug therapy ; immunology ; Humans ; Immune Tolerance ; drug effects ; Interferon-alpha ; metabolism ; Male ; Phytotherapy ; Plasma ; Young Adult

OBJECTIVETo explore the immunoregulatory effects of human amniotic mesenchymal cells (hAMCs) on allogeneic peripheral blood lymphocytes.

METHODSThe hAMCs were isolated from abandoned human amnion. Peripheral blood mononuclear lymphocytes (PBMLs) were separated from healthy donors by density gradient centrifugation. Then, PBMLs were treated with phytohemagglutinin (PHA) and different concentrations of hAMCs. Proliferation effect of PBMLs was tested using MTS assay, and production of IFN-gamma and TNF-alpha by PBMLs was detected by ELISA.

RESULTShAMCs could remarkably inhibit the lymphocytes proliferation. When the ratios of hAMCs to PBMLs were 0.05: 1, 0.10 :1, 0.20: 1, the inhibitory rates of PBMLs proliferation were 16.91%, 20.83% and 28.19%, respectively. HAMCs also decreased the production of IFN-gamma and TNF-alpha by PBMLs in a dose-dependent manner (P<0.01).

CONCLUSIONSHAMCs could inhibit the proliferation of allogeneic lymphocytes and reduce secretion of IFN-gamma and TNF-alpha, which might be one of the mechanism for prevention and remission of transplant rejection.

Amnion ; cytology ; Cell Proliferation ; Humans ; Immune Tolerance ; Interferon-gamma ; biosynthesis ; Lymphocyte Activation ; immunology ; Lymphocytes ; cytology ; drug effects ; immunology ; Mesoderm ; cytology ; Phytohemagglutinins ; immunology ; Tumor Necrosis Factor-alpha ; biosynthesis

This study was aimed to investigate the effect of 1,25(OH)(2) vitamin D(3) [1,25(OH)(2) Vit D(3)] on the differentiation, maturation and function of human dendritic cells (DC) in vitro and its mechanism. Human peripheral blood mononuclear cells were induced to differentiate to DC in vitro. The DC in test group were cultured with 1,25(OH)(2) Vit D(3) 1 nmol/L for 9 d, while the DC in control group were cultured with the equivalent of absolute alcohol. The expression of co-stimulatory molecules on DC were analyzed by flow cytometry. T cell proliferation induced by DC was assessed by MTT method. The expression of indoleamine 2, 3-dioxygenase (IDO) protein was determined by Western blot. The results showed that compared with the control group, the expression of CD80, CD83 and CD86 on DC in test group was significantly down-regulated (P < 0.05), while the CD1a was up-regulated (P < 0.05). The expression rate of CD80, CD83, CD86, CD1a in test group were (40.43 ± 9.83)%, (20.04 ± 4.73)%, (14.45 ± 5.38)%, (58.48 ± 10.72)% respectively, while in control group were (29.36 ± 13.34)%, (35.91 ± 10.19)%, (27.15 ± 11.64)%, (72.20 ± 12.79)% respectively. Compared with the control group, 1,25(OH)(2) Vit D(3)-treated DC exhibited a markedly reduced ability to stimulate allogenic T cell proliferation and up-regulated IDO protein expression.It is concluded that 1,25(OH)(2) Vit D(3) efficiently inhibits the maturation of DC and DC-mediated T cell proliferation, which may be related to the up-regulation of IDO protein expression.
Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cholecalciferol ; pharmacology ; Dendritic Cells ; cytology ; immunology ; Flow Cytometry ; Humans ; Immune Tolerance ; drug effects ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; metabolism