scholarly journals In vivo evaluation of the efficacy of Sophora moorcroftiana alkaloids in combination with Bacillus Calmette–Guérin (BCG) treatment for cystic echinococcosis in mice

2017 ◽  
Vol 92 (6) ◽  
pp. 681-686 ◽  
Author(s):  
G. Zhang ◽  
J. Wang ◽  
Y. Luo ◽  
M. Yuan ◽  
Q. Gao ◽  
...  
Keyword(s):  
Cystic Echinococcosis ◽  
Secondary Infection ◽  
Serum Levels ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Intragastric Administration ◽  
Bacillus Calmette Guerin ◽  
In Vivo Evaluation ◽  
Sophora Moorcroftiana

AbstractHuman cystic echinococcosis is a widespread, chronic, endemic, helminthic zoonosis caused by larval tapeworms of the species Echinococcus granulosus. At present, there is no rational and effective therapy for patients with echinococcosis. The present study evaluated whether the combination of alkaloids from Sophora moorcroftiana seeds (SMSa2) and Bacillus Calmette–Guérin (BCG) was effective in the treatment of experimental echinococcosis. After 20 weeks of secondary infection with protoscoleces, mice were randomly allocated to five groups and treated for 6 weeks by daily intragastric administration of albendazole (ABZ, 100 mg/kg), SMSa2 (100 mg/kg), BCG (abdominal subcutaneous injection at 5 × 106 CFU), SMSa2 + BCG (100 mg/kg SMSa2 and 5 × 106 CFU BCG) or normal saline (untreated group), respectively. The results indicated a significant reduction in the weight of hydatid cysts in the SMSa2 + BCG group compared with the untreated, SMSa2 and BCG groups. The rate of inhibition of hydatid cyst growth in the SMSa2 + BCG group (76.1%) was obviously increased compared with that in the SMSa2 (25.7%) and BCG (26.6%) groups, respectively. Compared with the untreated control, the SMSa2 + BCG group showed a non-significant increase in serum interleukin-4 (IL-4). Furthermore, the serum levels of interferon-γ (IFN-γ) between the untreated and SMSa2 + BCG groups were not statistically different. Therefore, the combination of alkaloids from S. moorcroftiana seeds and BCG can reduce cyst burden and is an effective therapeutic regimen against echinococcosis.

Effects of the Japanese herbal medicine ‘Inchinko-to’ (TJ-135) on concanavalin A-induced hepatitis in mice

2000 ◽  
Vol 99 (5) ◽  
pp. 421-431 ◽  
Author(s):  
Masayoshi YAMASHIKI ◽  
Akihito MASE ◽  
Ichiro ARAI ◽  
Xian-Xi HUANG ◽  
Tsutomu NOBORI ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Concanavalin A ◽  
Serum Levels ◽  
Interferon Γ ◽  
Hepatic Necrosis ◽  
Interleukin 12 ◽  
Con A ◽  
Ifn Γ

Inchinko-to (TJ-135) is a herbal medicine consisting of three kinds of crude drugs, and in Japan it is administered mainly to patients with cholestasis. The present study evaluated the effects of TJ-135 on concanavalin A (con A)-induced hepatitis in mice in vivo and con A-induced cytokine production in vitro. When mice were pretreated with oral TJ-135 for 1 week before intravenous con A injection, the activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were significantly decreased 8 h after con A administration (-82%, -96% and -66% respectively). In histological investigations, sub-massive hepatic necrosis accompanying inflammatory cell infiltration was not observed in mice pretreated with TJ-135. Serum levels of interleukin-12 (IL-12), interferon-γ (IFN-γ) and IL-2 were significantly lower in mice pretreated with TJ-135 compared with controls, while IL-10 levels were higher in these mice. Intrasplenic IL-12 levels were significantly lower in mice pretreated with TJ-135, while intrasplenic IL-10 levels were higher in these mice. In vitro, IL-10 production by splenocytes was increased by the addition of TJ-135 to the culture medium, whereas the production of IL-12 and IFN-γ was inhibited. These results suggest that con A-induced hepatitis was ameliorated by pretreatment with TJ-135. With regard to the mechanism of these effects of TJ-135, we speculate that TJ-135 inhibits the production of inflammatory cytokine and enhances the production of anti-inflammatory cytokines. Therefore administration of TJ-135 may be useful in patients with severe acute hepatitis accompanying cholestasis or in those with autoimmune hepatitis.

scholarly journals Increased serum levels of interleukin-6 in erythema nodosum leprosum suggest its use as a biomarker

2021 ◽  
Vol 87 ◽  
pp. 190-198
Author(s):  
Fátima Regina Vilani-Moreno ◽  
Vânia Nieto Brito-de-Souza ◽  
Sônia Maria Usó Ruiz Silva ◽  
Adriana Sierra Assêncio Almeida Barbosa ◽  
Beatriz Gomes Carreira Sartori ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Interleukin 17 ◽  
Erythema Nodosum Leprosum ◽  
Multibacillary Leprosy ◽  
Necrosis Factor

Background: Erythema nodosum leprosum (ENL) is a frequent complication of multibacillary leprosy that can result in significant morbidity, including peripheral nerve damage and physical disability. The identification of possible serum markers could be a valuable tool for the early detection of ENL. Aims: The purpose of this study was to evaluate selected serum mediators involved in the innate and adaptive immune responses to identify possible immunomarkers for ENL. Methods: The levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-17, interferon-γ, tumor necrosis factor, nitric oxide and anti-phenolic glycolipid-I antibodies were measured in the sera of leprosy patients with ENL [at the beginning of reaction (M0) and 1 month later (M1)], and then compared with the levels of the same markers in patients with untreated multibacillary leprosy without ENL (controls with leprosy: CTRL) and healthy individuals (healthy controls: CTRH). Results: Significantly higher levels of serum interleukin-6 were observed in M0 than in CTRL. In addition, pairwise comparisons showed higher levels of interleukin-6 in M0 compared to M1. Levels of tumor necrosis factor were higher in M0 than in CTRL, with no significant difference between M0 and M1. There were no differences in the levels of interleukin-2, interleukin-4, interleukin-10, interleukin-17 or interferon-γ between groups. The CTRL group had higher levels of nitric oxide compared to M0 and M1. High levels of anti-phenolic glycolipid-I were observed in M0, M1 and CTRL than in CTRH. Limitations: Three patients were not assessed at M1, decreasing the number of evaluated patients from 14 to 11. Conclusion: High-serum levels of interleukin-6 were observed during ENL, primarily in patients with more severe reactions; levels decreased after specific therapy, suggesting a role for this cytokine in pathogenesis and its utility as an ENL biomarker. Further studies should explore whether interleukin-6 could also be used as a predictive marker for ENL or as a specific target for its treatment.

Monokine Induced by Interferon-γ (MIG) Serum Levels Are a Marker of Disease Load and Correlate with Prognosis in Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5040-5040
Author(s):  
Martin Schreder ◽  
Gudrun Koch ◽  
Daniel Heintel ◽  
Kathrin Strasser-Weippl ◽  
Katrin Frischmuth ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Significance ◽  
Serum Levels ◽  
Interferon Γ ◽  
Serum Samples ◽  
Myeloma Cells ◽  
Autocrine Loop ◽  
Protein Levels

Abstract Background and Aims: Monokine-induced by interferon-γ (MIG) is a chemokine that is produced by monocytes and macrophages in response to interferon-γ and acts as a chemoattractant mainly to T-lymphocytes in inflammatory processes. MIG has also been suggested to act in an autocrine loop to stimulate tumour cells through its receptor CXCR3, which is known to be expressed in myeloma cells. However, it is presently unclear if MIG is of biologic significance in myeloma in vivo. We have recently shown that multiple myeloma oncogene 1 (MUM1) expression in myeloma cells correlates with prognosis in this disease (Heintel D et al., ASH 2005), and MUM1 was found to upregulate MIG gene expression in B cell malignancies (Uranishi M et al., Leukemia 2005). This led us to evaluate the potential prognostic significance of MIG serum levels in a series of well characterized myeloma patients. Methods: 105 newly diagnosed multiple myeloma patients (median age 69.3 years, range 39.4–90.5) were enrolled. 18 patients presented with Durie/Salmon stage I disease, 9 had stage II and 78 had stage III. MIG serum levels were determined by a commercially available ELISA (R&D Systems). Serum samples from 17 MGUS patients and 37 age-matched healthy volunteers were used as controls. Results: MIG serum levels were elevated in multiple myeloma patients (median 161.3 pg/ml, range 9.37–1966.0) compared to MGUS patients (median 92.7 pg/ml, range 6.29–1303.1) and healthy controls (median 106.2 pg/ml, range 51.0–390.6). For analysis of myeloma cases, a cut-off level for MIG of 200pg/ml (=95th percentile of MIG in controls) was chosen to identify low and high MIG expressers. Using the cut-off as defined above, 63 patients with low MIG serum levels and 42 high MIG expressers were identified in a population of 105 myeloma patients. MIG serum levels in myeloma patients showed strong correlations with several markers of tumour load including low albumin and high β2-microglobulin. Interestingly, no correlation was found with C-reactive protein levels, indicating that MIG is not associated with an inflammatory response in myeloma. Median survival was significantly shorter in patients with high MIG serum levels compared to patients with low MIG expression (median not reached vs. 17.0 months, p<0.001; see figure). Conclusions: MIG serum levels correlate with markers of disease burden in myeloma and high MIG levels are associated with a poor outcome in this disease. Overall Survival: low vs. high MIG serum levels Overall Survival: low vs. high MIG serum levels

Differential production of interferon-γ and interleukin-4 in response to Th1- and Th2-stimulating pathogens by γδ T cells in vivo

Nature ◽  
1995 ◽  
Vol 373 (6511) ◽  
pp. 255-257 ◽  
Author(s):  
David A. Ferrick ◽  
Mark D. Schrenzel ◽  
Thera Mulvania ◽  
Beryl Hsieh ◽  
Walter G. Ferlin ◽  
...  
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Th1 And Th2

scholarly journals Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells.

1990 ◽  
Vol 172 (3) ◽  
pp. 921-929 ◽  
Author(s):  
G Le Gros ◽  
S Z Ben-Sasson ◽  
R Seder ◽  
F D Finkelman ◽  
W E Paul
Keyword(s):  
T Cells ◽  
Serum Levels ◽  
Interleukin 4 ◽  
Cell Populations ◽  
Limited Capacity ◽  
Ifn Gamma ◽  
Striking Increase

T cell populations derived from naive mice produce very small amounts of interleukin 4 (IL-4) in response to stimulation on anti-CD3-coated dishes. IL-4 production by such cells is mainly found among large- and intermediate-sized T cells and is dependent upon IL-2. Injection of anti-IgD into mice, a stimulus that leads to striking increases in serum levels of IgG1 and IgE, causes a striking increase in the IL-4-producing capacity of T cells. This increase is first observed 4 d after injection of anti-IgD. IL-4 production by T cells from anti-IgD-injected donors is mainly found among large- and intermediate-sized T cells. Small, dense T cells are poor producers of IL-4. The capacity of T cells from anti-IgD-injected donors to produce IL-4 is enhanced by addition of IL-2 and is largely, but not completely, inhibited by neutralization of in situ produced IL-2. These results indicate that the control of IL-4 production in T cells from naive and anti-IgD-injected donors is similar. However, it is possible that a portion of the IL-4-producing activity of T cells from activated donors is IL-2 independent. Although small T cells from naive donors have a very limited capacity to produce IL-4 in response to stimulation with anti-CD3, even in the presence of added IL-2, they can give rise to IL-4-producing cells upon in vitro culture on plates coated with anti-CD3 if both IL-2 and IL-4 are added. This leads to the appearance of IL-4-producing cells within 2 d. When analyzed after 5 d of culture by harvesting and re-exposure to anti-CD3-coated culture wells and IL-2, these cells have increased their IL-4-producing capacity by approximately 100-fold. The development of IL-4-producing cells in response to anti-CD3, IL-2, and IL-4 is not inhibited by interferon gamma (IFN-gamma), nor does IFN-gamma diminish IL-4 production by these cells upon challenge with anti-CD3 plus IL-2.

scholarly journals Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers

2000 ◽  
Vol 192 (5) ◽  
pp. 741-754 ◽  
Author(s):  
Jennifer L. Matsuda ◽  
Olga V. Naidenko ◽  
Laurent Gapin ◽  
Toshinori Nakayama ◽  
Masaru Taniguchi ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Cell Receptor ◽  
Interferon Γ ◽  
Cell Number ◽  
Interleukin 4 ◽  
Regulatory Function ◽  
Nk T Cells ◽  
Lipid Antigen

A major group of natural killer (NK) T cells express an invariant Vα14+ T cell receptor (TCR) specific for the lipoglycan α-galactosylceramide (α-GalCer), which is presented by CD1d. These cells may have an important immune regulatory function, but an understanding of their biology has been hampered by the lack of suitable reagents for tracking them in vivo. Here we show that tetramers of mouse CD1d loaded with α-GalCer are a sensitive and highly specific reagent for identifying Vα14+ NK T cells. Using these tetramers, we find that α-GalCer–specific T lymphocytes are more widely distributed than was previously appreciated, with populations of largely NK1.1− but tetramer-binding T cells present in the lymph nodes and the intestine. Injection of α-GalCer leads to the production of both interferon γ and interleukin 4 by nearly all NK T cells in the liver and the majority of the spleen within 2 h. These cells mostly disappear by 5 h, and they do not reappear after 1 wk. Curiously, tetramer-positive thymocytes do not rapidly synthesize cytokines, nor do they undergo decreases in cell number after lipid antigen stimulation, although they express equivalent TCR levels. In summary, the data presented here demonstrate that α-GalCer–specific NK T cells undergo a unique and highly compartmentalized response to antigenic stimulation.

scholarly journals A Novel Microspheres Formulation of Puerarin: Pharmacokinetics Study and In Vivo Pharmacodynamics Evaluations

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao Song ◽  
Xihui Bai ◽  
Shiyu Liu ◽  
Linjuan Dong ◽  
Hui Deng ◽  
...  
Keyword(s):  
Protective Effect ◽  
Myocardial Injury ◽  
B Cell Lymphoma ◽  
Serum Levels ◽  
Intragastric Administration ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Promising Candidate ◽  
Oral Preparation ◽  
Total Superoxide Dismutase

The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of puerarin loaded carboxymethyl chitosan microspheres (Pue-CCMs). The differences in pharmacokinetics parameters of rats after intragastric administration of Pue-CCMs and puerarin were investigated using HPLC. To assess the protective effect of Pue-CCMs on myocardial injury in rats, serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were measured, in addition to pathological examinations and immunohistochemical staining. Our present study has shown that the AUC0–t, Cmax, Tmax, MRT0–t of Pue-CCMs, and puerarin were 20.176 mg·h/L, 3.778 μg/mL, 1 h, 4.634 h and 9.474 mg·h/L, 2.618 μg/mL, 0.542 h, and 3.241 h, respectively. Pue-CCMs alleviated myocardial ischemic injury. Pretreatment with Pue-CCMs could significantly decrease CK, LDH, and MDA levels and increase T-SOD level in the serum. Pue-CCMs downregulated expression of the Bcl-2 associated X protein (Bax) and upregulated B-cell lymphoma-2 (Bcl-2) expression. Compared with puerarin group, the Pue-CCMs group could improve the oral bioavailability of puerarin. The protective effect of Pue-CCMs against myocardial injury was significantly greater than puerarin at the same dose. In summary, Pue-CCMs should be a qualified and promising candidate as a new oral preparation of puerarin.

scholarly journals Immunoprotective effect of an in silico designed multiepitope cancer vaccine with BORIS cancer-testis antigen target in a murine mammary carcinoma model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elham Mahdevar ◽  
Amirhosein Kefayat ◽  
Ashkan Safavi ◽  
Amirhossein Behnia ◽  
Seyed Hossein Hejazi ◽  
...  
Keyword(s):  
Cancer Vaccine ◽  
Mammary Carcinoma ◽  
Peptide Vaccine ◽  
Serum Levels ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Cancer Testis Antigen ◽  
Strong Immune Response ◽  
Weight Decrease ◽  
Cancer Testis

AbstractIn our previous study, immunoinformatic tools were used to design a novel multiepitope cancer vaccine based on the most immunodominant regions of BORIS cancer-testis antigen. The final vaccine construct was an immunogenic, non-allergenic, and stable protein consisted of multiple cytotoxic T lymphocytes epitopes, IFN-γ inducing epitopes, and B cell epitopes according to bioinformatic analyzes. Herein, the DNA sequence of the final vaccine construct was placed into the pcDNA3.1 vector as a DNA vaccine (pcDNA3.1-VAC). Also, the recombinant multiepitope peptide vaccine (MPV) was produced by a transfected BL21 E. coli strain using a recombinant pET-28a vector and then, purified and screened by Fast protein liquid chromatography technique (FPLC) and Western blot, respectively. The anti-tumor effects of prophylactic co-immunization with these DNA and protein cancer vaccines were evaluated in the metastatic non-immunogenic 4T1 mammary carcinoma in BALB/c mice. Co-immunization with the pcDNA3.1-VAC and MPV significantly (P < 0.001) increased the serum levels of the MPV-specific IgG total, IgG2a, and IgG1. The splenocytes of co-immunized mice exhibited a significantly higher efficacy to produce interleukin-4 and interferon-γ and proliferation in response to MPV in comparison with the control. The prophylactic co-immunization regime caused significant breast tumors’ growth inhibition, tumors’ weight decrease, inhibition of metastasis formation, and enlarging tumor-bearing mice survival time, without any considerable side effects. Taking together, this cancer vaccine can evoke strong immune response against breast tumor and inhibits its growth and metastasis.

scholarly journals Specific panallergen peptide of Sorghum Polcalcin showing IgE response identified based on in silico and in vivo peptide mapping

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Chandra Sekhar Bokka ◽  
Ganesh Kumar Veeramachaneni ◽  
V.B.S.C. Thunuguntla ◽  
Naresh Kumar Manda ◽  
Jayakumar Singh Bondili
Keyword(s):  
In Silico ◽  
Peptide Mapping ◽  
Interferon Γ ◽  
Docking Studies ◽  
Antigenic Determinants ◽  
T Helper ◽  
In Vivo Evaluation ◽  
Ige Response ◽  
Helper Type

Abstract In India, Sorghum plant allergenicity was reported to be approximately 54.9%. Sorghum bicolor Polcalcin (Sorb PC) was identified as the panallergen but the specificity of this allergen is yet to be characterized. The present study was aimed to characterize the antigenic determinants of Sorb PC that are responsible for eliciting the IgE response. In silico modeling, simulation studies and docking of Sorb PC peptides (PC1–11) against IgG and IgE followed by in vivo evaluation was adopted. Peptide docking studies revealed PC 6 with highest G-score −12.85 against IgE followed by PC-11, 5, 1 and 7 (−10.91) peptides. The mice sensitized with PC7 peptide showed interleukin (IL) 4 (IL-4), IL-5, IL-12, TNF-α and GMCSF levels increased when compared with other peptides and controls, signifying a strong T helper type 2 (Th2)-based response. In tandem, the T helper type 1 (Th1) pathway was inhibited by low levels of cytokine IL-2, interferon γ (IFN-γ) and increased IL-10 levels justifying the role of PC7 in allergic IgE response. Considering the above data of overlapping peptides of PC6 and PC7, N-terminal part of the PC7 peptide (DEVQRMM) is found to play a crucial role in Sorghum Polcalcin allergenic response.

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