A new herbal composition. HemoHIM, was developed using irradiated animal models and was successfully applied as an immune-improving agent. In a view that the protection and recovery of immune, hematopoietic and self-renewal tissues are essential for radioprotective agents, HemoHIM was developed based on a novel combination of three edible herbs (Angelica Radix, Cnidii Rhizoma. Paeonin Radix) that meet all those requirements. HemoHIM significantly protected the immune and hematopoietic system and enhanced their recovery in y-irradiated mice. For the application of HemoHIM as a health functional food and a supplementary agent for the cancer patients, the efficacy of HemoHIM to improve the immune functions was further evaluated in immune-depressed animals and humans. Animal studies demonstrated that HemoHIM significantly improved the immune functions in cyclophosphamide-treated mice, aged mice, and dexamethasone-treated mice. In human studies, HemoHIM enhanced the immune activity and cytokine secretion in sub-healthy volunteers, and alleviated the severe leukocyre depression in cancer patients during radiation and chemotherapy. Based on these results, HemoHIM was approved by Korea FDA as a material of health functional food for immune function improvement and will be commercially available soon. This case of HemoHIM research and development suggested that irradiated animals can be good models for biological degenerations such as immune depression, self-renewal tissue damage, and aging for the development of biological modulators.
Interleukin-32 (IL-32) is a cytokine inducing crucial inflammatory cytokines such as tumor necrosis factor-${\alpha}(TNF{\alpha})$ and IL-6 and its expression is elevated in various inflammatory autoimmune diseases, certain cancers, as well as viral infections. IL-32 gene was first cloned from activated T cells, however IL-32 expression was also found in other immune cells and non-immune cells. IL-32 gene was identified in most mammals except rodents. It is transcribed as multiple-spliced variants in the absence of a specific activity of each isoform. IL-32 has been studied mostly in clinical fields such as infection, autoimmune, cancer, vascular disease, and pulmonary diseases. It is difficult to investigate the precise role of IL-32 in vivo due to the absence of IL-32 gene in mouse. The lack of mouse IL-32 gene restricts in vivo studies and restrains further development of IL-32 research in clinical applications although IL-32 new cytokine getting a spotlight as an immune regulatory molecule processing important roles in autoimmune, infection, and cancer. In this review, we discuss the regulation and function of IL-32 in inflammatory bowel diseases and rheumatoid arthritis.
In order to investigate the effect of Houttuynia cordata Thunb and Sanggukeum on immune function, the author performed this experimental study. Delayed type hypersensitivity (DTH) and rosette forming cells(RFC) for cell-mediated immune response, hemagglutinin (HA) titers, hemolysin (HL) titers and plaque forming cells (PFC) for humoral immune response, immunoglogbulin (Ig G) titer, splenic natural Killer cell activity (NKCA) carbon clearance for phagocytic function of MPS(mononuclear phagocyte system) and change of weight were measured in ICR mice. The results were summarized as follows ; 1. DTH was increased with statistical significance in all of the treated group as compared with the control group. 2. RFC was increased with statistical significance in case of Houttuynia cordata Thunb but in case of sanggukeum and gamisanggukeum valuable increase of RFC was not recognized as compared with the control group. 3. HA titers were increased with statistical significance in case of Houttuynia cordata Thunb but in cases of Sanggukeum and Gamisanggukeum HA titers were not recognized as compared with the control group. 4. HL titers were increased with statistical significance in case of Houttuynia cordata Thunb but in cases of Sanggukeum and Gamisanggukeum valuable increase of HL titer was not recognized as compared with the control group. 5. PFC was increased in all of the treated group but valuable increase of PFC was not recognized as compared with the controal group. 6. Ig G titers were increased in all of the treated group but valuable increase of Ig G titer was not recognized as compared with the control group. 7. NKCA was increased with statistical significance in case of Houttuynia cordate Thunb but in case of Sanggukeum and Gamisanggukeum valuable increase of NKCA was not recognized as compared with the control group. 8. Carbon clearance was increased with statistical significance in case of Sanggukeum but in case of Houttuynia cordata Thunb and Gamisanggukeum valuable increase of carbon clearance was not recognized as compared with the control group. 9. Change of weight was increased with statistical significance in all of the treated group. Through in vivo experimental study in ICR mice, Houttuynia cordata Thunb enhances the cell-mediated immune responce, the humoral immune responce and natural killer cell activity. And Houttuynia cordata Thunb enhances immune responce as compared with that plused Sanggukeum. Sanggukeum enhances carbon clearance and enhances a little cell-mediated immune responce, the humoral immune response and natural killer cell activity. According to the above results it seems Houttuynia cordata Thunb and Sanggukeum was able to use Infection, Inflammation and Tumor.
NecroX-7 is a novel small compound of the NecroX series based on the indole moiety, which has potent cytoprotective and antioxidant properties. We previously detected potential immune regulatory effects of NecroX-7 in immune related diseases like Graft-versus-Host Disease. However, the function and the underlying mechanisms of immunological effects of NecroX-7 in the immune system have not been well established. In this study, we investigated the immune response characterization of differentially expressed genes of NecroX-7 administration in $CD4^+$ T cells by microarray analysis. $CD4^+$ T cells stimulated with NecroX-7 ($40{\mu}M$) or vehicle for 72 hours resulted in the identification of 337 differentially expressed genes (1.5 fold, P<0.05) by expression profiling analysis. Twenty eight of the explored NecroX-7-regulated genes were related to immune system processes. These genes were validated by quantitative real-time PCR. The most significant genes were glutathione reductase, eukaryotic translation elongation factor 1, lymphotoxin-alpha, heat shock protein 9 and chloride intracellular channel protein 4. These findings demonstrate the strongly immune response of NecroX-7 in $CD4^+$ T cells, suggesting that cytoprotection and immune regulation may underlie the critical aspects of NecroX-7 exposure.
Alexandra A. Wolfarth;Swati Dhar;Jack B. Goon;Ugonna I. Ezeanya;Sara Ferrando-Martínez;Byung Ha Lee
IMMUNE NETWORK
/
v.22
no.1
/
pp.5.1-5.22
/
2022
The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short halflife of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.
The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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v.28
no.3
/
pp.14-29
/
2015
Objectives : The extract of Sagunja-tang has been traditionally used for restorative treatment of constitutional weakness, vascular and immune disorder, and nervous disease in Oriental country. This study investigated the regulatory effects of Sagunja-tang on the expression, production, and activity of immune mediators.Methods : In this study, the extract of Sagunja-tang was prepared by extracting with distilled water at 100$^{\circ}C$ for 2.5h. The extract was freeze-dried following filtration through 0.45${{\mu}m}$ filter. The extract was dissolved in Hank's balanced salt solution (HBSS) and filtered again through 0.45${{\mu}m}$ filter before use. The level of nitrite, an oxidative product of nitric oxide(NO) was measured in the culture medium by the Griess reaction. The levels of prostaglandin E2(PGE2), Th1 cytokines (IFN-${\gamma}$, IL-2) and Th2 cytokines(IL-4, IL-5, IL-13) were measured by enzyme-linked immunosorbent assay and the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were determined by Western blot analysis. Also examined the effects of the extract on T-cell proliferation and cytotoxic activity of natural killer cells.Results : In this investigation, Production levels of Th2 cytokines (IL-4, IL-5, IL-13) was inhibited in a dose dependent manner by treatment with the extract. I also found that the extract increased T-cell proliferation and cytotoxic activity of natural killer cells in a dose-dependent manner.Conculsions : These results suggest that the water extract of Sagunja-tang may be useful for a therapeutic drug against a sickly constitution and immune diseases, probably by regulating the production of immune mediators.
A five-week trial was conducted to evaluate the effect of organic chromium from different sources on growth performance, immune response and serum parameters of weaned pigs. One hundred and eighty Tianjin white pigs weaned at $35{\pm}1$ days of age, were allotted to three treatments with six replicates and10 pigs per pen. Pigs were fed corn-soybean-whey-fishmeal basal diets with either no supplemental Cr, $200{\mu}g/kg$ Cr as chromium picolinate (CrPi), or $200{\mu}g/kg$ Cr as chromium yeast (Cr-yeast). To assess humoral immune response, all pigs were immunized with swine fever virus on day 21 and two pigs from each pen were immunized with pure albumin on day 14. Cell-mediated immunity was measured by determining the double skinfold thickness (DST) of two pigs from each pen before and 24h after stimulation with phytohemagglutinin (PHA) on day 28. The results indicated that: (1) diets with Cr-yeast increased average daily gain (ADG, p<0.05) and tended to increase average daily feed intake (ADFI, p<0.10). Diets with CrPi did not increase ADG and ADFI (p>0.05). (2) Dietary CrPi or Cr-yeast supplementation did not affect blood urea nitrogen, glucose, or cholesterol (p>0.05), but blood urea nitrogen in CrPi and Cr-yeast supplemented groups and blood glucose in the Cr-yeast supplemented group were significantly influenced by sampling days (p<0.05). (3) Serum proteins (TP, ALB, and GLB) were influenced by sampling days (p<0.05), but not by dietary Cr treatment (p>0.10). (4) There were no significant differences among treatments in the titers of albumin antibody and swine fever virus antibody (p>0.05) or DST before and after PHA stimulation (p>0.05), indicating that organic chromium has no significant effect on the immune function of weaning pigs. Therefore, these results agree with other research that the effects of supplemental Cr are variable in weanling pigs.
Kim, Hye-Nam;Lee, Jung-Nam;Kim, Gi-Eun;Ha-Lee, Young-Mie;Kim, Chan-Wha;Sohn, Jeong-Won
Journal of Microbiology and Biotechnology
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v.9
no.6
/
pp.826-831
/
1999
${\beta}-Glucan$, one of the major cell wall components of Saccharomyces cerevisiae, is known to enhance the immune function, especially by activating macrophages. Accordingly, in an effort to develop a safe and efficient immune stimulatory agent, we prepared crude ${\beta}-glucan$ (glucan-p1) and partially purified ${\beta}-glucan$ that was free of mannoproteins (glucan-p2), and evaluated their effect on both the macrophage function and resistance to E. coli-induced peritonitis. To investigate the function of the macrophages, phagocytosis, $TNF-{\alpha}$ secretion, oxygen burst, and the expression of cytokine genes such as $IFN-{\gamma}$ and IL-12 were analyzed. Glucan-p2 markedly stimulated the macrophages with all these parameters. Glucan-p1, however, did not stimulate phagocytosis, yet it induced $TNF-{\alpha}$ secretion, oxygen burst, and the expression of $IFN-{\gamma}$ and IL-12, although less efficiently than glucan-p2. Finally, to test the in vivo protective effect of {\beta}-glucan against infection, the survival of mice from E. coli-induced peritonitis was investigated. After 24 h of the peritoneal challenge of E. coli, all of the mice treated with glucan-p2 survived whereas none survived in the control group. Glucan-p1 showed only a marginal effect in protecting the mice. These results suggest that mannoprotein-free gluean-p2, but not gluean-p1, can serve as an effective immune-stimulating agent.
Cell therapy applied to wound healing or tissue regeneration presents a revolutionary realm to which principles of gene engineering and delivery may be applied. One promising application is the transplantation of cells into the wounded tissue to help the tissue repair. However, when cells are transplanted from in vitro to in vivo, immune rejection occurs due to the immune response triggered by the activation of T-cell, and the transplanted cells are destroyed by the attack of activated T-cell and lose their function. Immune suppressant such as FK506 is commonly used to suppress immune rejection during transplantation. However, such kind of immune suppressants not only suppresses immune rejection in the periphery of transplanted cells but also suppresses whole immune response system against pathogenic infection. In order to solve this problem, we developed a method to protect the desired cells from immune rejection without impairing whole immune system during cell transplantation. Previously, we reported the success of constructing glomerular epithelial cells for removal of immune complex, in which complement receptor of type 1 (CR1) was over-expressed on the membrane of renal glomerular epithelial cells and could bind immune complex of DNA/anti-DNA-antibody to remove immune complex through phagocy-tosis [1]. Attempting to apply the CR1-expressing cells to cell therapy and evade immune rejection during cell transplantation, we constructed three plasmids containing genes encoding a soluble fusion protein of cytolytic T lymphocyte associated antigen-4 (CTLA4Ig) and an enhanced green fluorescent protein (EGFP). The plasmids were transfected to the above-mentioned glomerular epithelial cells to express both genes simultaneously. Using the clone cells for cell transplantation showed that mice with autoimmune disease prolonged their life significantly as compared with the control mice, and two injections of the cells at the beginning of two weeks resulted in remarkable survivability, whereas it requires half a year and 50 administrations of proteins purified from the same amount of cells to achieve the same effect.
Proceedings of the Korean Society for Noise and Vibration Engineering Conference
/
1998.04a
/
pp.273-279
/
1998
An immune system has powerful abilities such as memory, recognition and learning to respond to invading antigens, and is applied to many engineering algorithm recently. In this paper, the combined optimization algorithm is proposed for multi-optimization problem by introducing the capability of the immune system that controls the proliferation of clones to the genetic algorithm. The optimizing ability of the proposed optimization algorithm is identified by using two multi-peak functions which have many local optimums and optimization of the unbalance response function for rotor model.
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