Stimulation Of Immune Reactions Research Articles

Corrigendum: Zoledronate Triggers Vδ2 T Cells to Destroy and Kill Spheroids of Colon Carcinoma: Quantitative Image Analysis of Three-Dimensional Cultures.

[This corrects the article on p. 998 in vol. 9, PMID: 29867975.].

Zoledronate Triggers Vδ2 T Cells to Destroy and Kill Spheroids of Colon Carcinoma: Quantitative Image Analysis of Three-Dimensional Cultures.

New successful anti-cancer strategies are based on the stimulation of immune reaction against tumors: however, preclinical testing of such treatments is still a challenge. To improve the screening of anti-cancer drugs, three-dimensional (3D) culture systems, including spheroids, have been validated as preclinical models. We propose the spheroid 3D system to test anti-tumor drug-induced immune responses. We show that colorectal carcinoma (CRC) spheroids, generated with the epithelial growth factor (EGF), can be co-cultured with Vδ2 T cells to evaluate the anti-tumor activity of these effector lymphocytes. By computerized image analysis, the precise and unbiased measure of perimeters and areas of tumor spheroids is achievable, beside the calculation of their volume. CRC spheroid size is related to ATP content and cell number, as parameters for cell metabolism and proliferation; in turn, crystal violet staining can check the viability of cells inside the spheroids to detect tumor killing by Vδ2 T cells. In this 3D cultures, we tested (a) zoledronate that is known to activate Vδ2 T cells and (b) the therapeutic anti-EGF receptor humanized antibody cetuximab that can elicit the antibody-dependent cytotoxicity of tumor cells by effector lymphocytes. Zoledronate triggers Vδ2 T cells to kill and degrade CRC spheroids; we detected the T-cell receptor dependency of zoledronate effect, conceivably due to the recognition of phosphoantigens produced as a drug effect on target cell metabolism. In addition, cetuximab triggered Vδ2 T lymphocytes to exert the antibody-dependent cellular cytotoxicity of CRC spheroids. Finally, the system reveals differences in the sensitivity of CRC cell lines to the action of Vδ2 T lymphocytes and in the efficiency of anti-tumor effectors from distinct donors. A limitation of this model is the absence of cells, including fibroblasts, that compose tumor microenvironment and influence drug response. Nevertheless, the system can be improved by setting mixed spheroids, made of stromal and cancer cells. We conclude that this type of spheroid 3D culture is a feasible and reliable system to evaluate and measure anti-tumor drug-induced immune responses beside direct anti-cancer drug effect.

Addition of Selenium Improves Immunomodulative Effects of Glucan.

Background:Selenium (Se) is an established essential nutrient that plays a role in various biological processes including cancer development. Similarly, stimulation of immune reactions by β-glucans is well-documented.Aims:In the current study, we focused on the stimulation of phagocytosis and interleukin (IL)-2 production and on potentiation of anticancer immunity by a combination of glucan with two types of Se.Materials and Methods:Phagocytosis was evaluated using synthetic microspheres; cancer development was measured either using breast cancer cells or using lung cancer cells.Results:Using two different murine models of cancer, we showed that the Se/glucan combination strongly suppressed the growth of cancer, mostly probably via stimulation of immunity.Conclusions:A combination of glucan with Se offers superior stimulation of immunity and inhibition of cancer growth.

Resveratrol/Glucan/Vitamin C combination offers strong stimulation of immunity

Natural products, useful in preventing and/or treating various diseases, have been sought after throughout the history of mankind. The longest history as immunomodulators belongs to beta glucans. Despite the demonstrated activity of various glucans, the search for optimalization of their biological effects still continues. Recently, numerous substances have been shown to have synergistic effects with glucans. We decided to compare the biological activities of insoluble yeast-derived β1,3-D-glucan with a combination of glucan/resveratrol/vitamin C. Our data show that whereas resveratrol or vitamin C alone had only limited (if any) effects on immune reactions, the combination significantly increased the phagocytosis of peripheral blood leukocytes, specific antibody response, nitrite anion production and apoptosis. This combination also showed strong effects on immunosuppression caused by various toxins. In addition, significant inhibition of cancer growth was found using two different experimental models. We can summarize that whereas resveratrol or vitamin C alone had only limited effects on immune reactions, the combination significantly increased all tested immunological reactions. Our data represent further proof that combined preparations of glucan, resveratrol and vitamin C strongly stimulate the immune reactions. We hypothesize that strong anti-cancer properties showed by the combination of these three compounds are manifested via stimulation of immune reactions and apoptosis. A study attempting to reveal the exact mechanisms of these effects is currently under progress.

Immune-enhancing effects of Maitake (Grifola frondosa) and Shiitake (Lentinula edodes) extracts.

The role of glucan in stimulation of immune reactions has been studied for several decades. In this report, we focused on the effects of orally administered glucan Maitake and Shiitake on immune reactions. We measured phagocytosis, NK cell activity, and secretion of IL-6, IL-12, IFN-γ as well as C-reactive protein (CRP) after 14 days of oral application of tested glucans. For comparison, active hexose correlated compound (AHCC) was used in all reactions. We found significant stimulation of defense reaction. In all cases, the most active was the Maitake-Shiitake combination, with Maitake alone being the second strongest, followed by Shiitake on its own and AHCC. Short-term oral application of natural immunomodulating glucans from Maitake and Shiitake mushrooms strongly stimulated both the cellular and humoral branch of immune reactions. These activities were significantly higher than those of AHCC.

Clinical trials of yeast-derived β-(1,3) glucan in children: effects on innate immunity.

The role of glucan in the stimulation of immune reactions is well established. In our report, we focused on the effects of orally administered glucan on nonspecific immunity of children with chronic respiratory problems. We measured the levels of albumin, lysozyme. C-reactive protein (CRP) and calprotectin in the saliva of 60 children ages 8-12 years and evaluated the effects of 30-day treatment with 100 mg/d oral dose of glucan. We found a significant increase in the production of lysozyme, CRP and calprotectin in glucan-treated children. Short-term oral application of natural immunomodulator β-glucan significantly stimulated mucosal immunity of children with chronic respiratory problems.

Placebo-driven clinical trials of yeast-derived β-(1-3) glucan in children with chronic respiratory problems.

The role of glucan in stimulation of immune reactions has been studied for several decades. In this report we focused on the effects of orally administered glucan in children with chronic respiratory problems. We measured the levels of albumin, lysozyme and CRP in saliva of 40 children aged 8-12 years and evaluate the effects of 100 mg/d oral dose of glucan. We found a significant increase in production of changes in production of lysozyme and CRP in glucan-treated children. In addition, a strong improvement in general conditions was found. Short-term oral application of natural immunomodulator β-glucan stimulated mucosal immunity of children with chronic respiratory problems.

PLACEBO-DRIVEN CLINICAL TRIALS OF TRANSFER POINT GLUCAN #300 IN CHILDREN WITH CHRONIC RESPIRATORY PROBLEMS: III. CLINICAL FINDINGS

The role of glucan in stimulation of immune reactio ns has been studied for decades. In this report we focused on the effects of orally administered gluca n in children with chronic respiratory problems. We measured the physical endurance using a 6MWT test and the levels of eNO in 50 children aged 8-12 years and evaluated the effects of 100 mg/d oral dose of glucan. We found significant improvements in physical indurance and exhaled nitric oxide in glucan-treate d children. In addition, strong improvements in gen eral conditions were found. Short-term oral application of natural immunomodulator β-glucan enhancers the overall health and regulation of energetic metaboli sm in children with chronic respiratory problems.

PLACEBO-DRIVEN CLINICAL TRIALS OF TRANSFER POINT GLUCAN #300 IN CHILDREN WITH CHRONIC RESPIRATORY PROBLEMS: ANTIBODY PRODUCTION

The role of glucan in stimulation of immune reactio ns has been well-established. In this report, we fo cused on the antibody production in glucan-supplemented children with chronic respiratory problems. We measured the levels of salivary IgA, IgM and IgG in 40 children aged 8-12 years and evaluated the effe cts of 100 mg d -1 oral dose of glucan. We found a significant increa se in production of all tested antibodies in the glucan-stimulated group, but a decrease of anti body production in the control group. A thirty-day oral application of yeast-based natural immunomodulator β-glucan strongly stimulated the mucosal immunity of children with chronic respiratory problems.

Is therapeutic hypothermia immunosuppressive?

Is therapeutic hypothermia immunosuppressive?

Glucan and resveratrol complex - possible synergistic effects on immune system

Recent data showing that glucan elicited defense responses in grapevine and induced protection via induction of resveratrol production led us to evaluate the possible synergetic effects of glucan and resveratrol complex on immune reactions. We measured phagocytosis using HEMA particles, expression of cell surface markers via fl ow cytometry, expression of cytokines using ELISA, recovery after fluorouracil-induced leucopenia and effects on gene expression via RT-PCR. Our results showed that both glucan and resveratrol complex stimulated phagocytosis of blood leukocytes, caused increase in surface expression of CD(+) splenocytes and showed higher restoration of spleen recovery after experimentally induced leucopenia. In all these cases, strong synergetic effects were observed. When we measured the effects of these substances on expression level of NF-kappaB2, Cdc42 and Bcl-2 in breast cancer cells, upregulation of Cdc42 expression was evident only using both immunomodulators in combination. In conclusion, our data suggest significant synergy in stimulation of immune reactions and support further studies of these natural immunomodulators.

The role of dopaminergic system in the immunostimulatory effects of substance P and its analog

Systemic administration of synthetic substance P or its analog EC-1 to CBA mice results in considerable stimulation of immune reactions. No stimulation is observed after disconnection of the hypothalamus from the pituitary. It is concluded that the immunostimulating effect of these peptides is mediated by the dopaminergic system, since it is abolished by the D2 receptor blocker haloperidol.

Immune response to cyclin B1 in hepatocellular carcinoma

Proteins expressed by plasmids encoding human cyclins and cyclin-dependent kinase 2 (CDK2) were used as antigens in immunoblotting. Fifteen of 100 patients with hepatocellular carcinoma (HCC) were found to have autoantibodies reactive with cyclin B1 and with a 40-kd degradation product of cyclin B1-glutathione-S-transferase (GST) fusion protein. Only one serum was found to react with cyclin A and another single serum with CDK2 but no antibodies were detected to cyclin D1 and E. The basis for autoimmune responses to cyclin B1 in HCC are unknown at the present time but the possibilities might include aberrations in cyclin B1 regulation leading to altered product or its expression which resulted in stimulation of immune reactions.(Hepatology 1997 Jan;25(1):75-80)

Immune response to cyclin B1 in hepatocellular carcinoma.

Proteins expressed by plasmids encoding human cyclins and cyclin-dependent kinase 2 (CDK2) were used as antigens in immunoblotting. Fifteen of 100 patients with hepatocellular carcinoma (HCC) were found to have autoantibodies reactive with cyclin B1 and with a 40-kd degradation product of cyclin B1-glutathione-S-transferase (GST) fusion protein. Only one serum was found to react with cyclin A and another single serum with CDK2 but no antibodies were detected to cyclin D1 and E. The basis for autoimmune responses to cyclin B1 in HCC are unknown at the present time but the possibilities might include aberrations in cyclin B1 regulation leading to altered product or its expression which resulted in stimulation of immune reactions.

Cytokines in the Healthy and Diseased Brain

Under noninflammatory conditions, interleukin-1 and interleukin-6 are located in neurons and glial cells of discrete brain regions;they appear to be expressed at a constant level during peripheral immune challenges. After severe brain damage, however, synthesis in neurons and glia is increased with stimulation of immune reactions, gliosis, and neuronal growth.