The Unitary Micro-Immunotherapy Medicine Interferon-γ (4 CH) Displays Similar Immunostimulatory and Immunomodulatory Effects than Those of Biologically Active Human Interferon-γ on Various Cell Types.

As a cytokine, gamma-interferon (IFN-γ) is considered a key player in the fine-tuned orchestration of immune responses. The extreme cellular sensitivity to cytokines is attested by the fact that very few of these bioactive molecules per cell are enough to trigger cellular functions. These findings can, at least partially, explain how/why homeopathically-prepared cytokines, and especially micro-immunotherapy (MI) medicines, are able to drive cellular responses. We focused our fundamental research on a unitary MI preparation of IFN-γ, specifically employed at 4 CH, manufactured and impregnated onto sucrose-lactose pillules as all other MI medicines. We assessed the IFN-γ concentration in the medium after dilution of the IFN-γ (4 CH)-bearing pillules and we evaluated in vitro drug responses in a wide range of immune cells, and in endothelial cells. Our results showed that IFN-γ (4 CH) stimulated the proliferation, the activation and the phagocytic capabilities of primary immune cells, as well as modulated their cytokine-secretion and immunity-related markers' expression in a trend that is quite comparable with the well-recognized biological effects induced by IFN-γ. Altogether, these data provide novel and additional evidences on MI medicines, and specifically when active substances are prepared at 4 CH, thus suggesting the need for more investigations.

Reviewing the Etiologic Agents, Microbe-Host Relationship, Immune Response, Diagnosis, and Treatment in Chromoblastomycosis.

Chromoblastomycosis (CBM) is a neglected human disease, caused by different species of pigmented dematiaceous fungi that cause subcutaneous infections. This disease has been considered an occupational disease, occurring among people working in the field of agriculture, particularly in low-income countries. In 1914, the first case of CBM was described in Brazil, and although efforts have been made, few scientific and technological advances have been made in this area. In the field of fungi and host cell relationship, a very reduced number of antigens were characterized, but available data suggest that ectoantigens bind to the cell membrane of host cells and modulate the phagocytic, immunological, and microbicidal responses of immune cells. Furthermore, antigens cleave extracellular proteins in tissues, allowing fungi to spread. On the contrary, if phagocytic cells are able to present antigens in MHC molecules to T lymphocytes in the presence of costimulation and IL-12, a Th1 immune response will develop and a relative control of the disease will be observed. Despite knowledge of the resistance and susceptibility in CBM, up to now, no effective vaccines have been developed. In the field of chemotherapy, most patients are treated with conventional antifungal drugs, such as itraconazole and terbinafine, but these drugs exhibit limitations, considering that not all patients heal cutaneous lesions. Few advances in treatment have been made so far, but one of the most promising ones is based on the use of immunomodulators, such as imiquimod. Data about a standard treatment are missing in the medical literature; part of it is caused by the existence of a diversity of etiologic agents and clinical forms. The present review summarizes the advances made in the field of CBM related to the diversity of pathogenic species, fungi and host cell relationship, antigens, innate and acquired immunity, clinical forms of CBM, chemotherapy, and diagnosis.

Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment.

Coronavirus (SARS-CoV-2) is spreading rapidly in the world and is still taking a heavy toll. Studies show that cytokine storms and imbalances in T-helper (Th)1/Th2 play a significant role in most acute cases of the disease. A number of medications have been suggested to treat or control the disease but have been discontinued due to their side effects. Melatonin, as an intrinsic molecule, possesses pharmacological anti-inflammatory and antioxidant properties that decreases in concentration with age; as a result, older people are more prone to various diseases. In this study, patients who were hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) were given a melatonin adjuvant (9 mg daily, orally) for fourteen days. In order to measure markers of Th1 and Th2 inflammatory cytokines (such as interleukin (IL)-2, IL-4, and interferon (IFN)-γ) as well as the expression of Th1 and Th2 regulatory genes (signal transducer and activator of transcription (STAT)4, STAT6, GATA binding protein 3 (GATA3), and T-box expressed in T cell (T-bet)), blood samples were taken from patients at the beginning and end of the treatment. Adjuvant therapy with melatonin controlled and reduced inflammatory cytokines in patients with COVID-19. Melatonin also controlled and modulated the dysregulated genes that regulate the humoral and cellular immune systems mediated by Th1 and Th2. In this study, it was shown for the first time that melatonin can be used as a medicinal adjuvant with anti-inflammatory mechanism to reduce and control inflammatory cytokines by regulating the expression of Th1 and Th2 regulatory genes in patients with COVID-19.

Propolis antiviral and immunomodulatory activity: a review and perspectives for COVID-19 treatment.

OBJECTIVES: Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a bee-made product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords "propolis", "virus", "antiviral", "antimicrobial" and "coronavirus". KEY FINDINGS: Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines. SUMMARY: Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals' immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19.

Yin and Yang: The dual effects of interferons on hematopoiesis.

Interferons are an ancient and well-conserved group of inflammatory cytokines most famous for their role in viral immunity. A decade ago, we discovered that interferons also play an important role in the biology of hematopoietic stem cells (HSCs), which are responsible for lifelong blood production. Though we have learned a great deal about the role of interferons on HSC quiescence, differentiation, and self-renewal, there remains some controversy regarding how interferons impact these stem cells, with differing conclusions depending on experimental models and clinical context. Here, we review the contradictory roles of Type 1 and 2 interferons in hematopoiesis. Specifically, we highlight the roles of interferons in embryonic and adult hematopoiesis, along with short-term and long-term adaptive and maladaptive responses to inflammation. We discuss experimental challenges in the study of these powerful yet short-lived cytokines and strategies to address those challenges. We further review the contribution by interferons to disease states including bone marrow failure and aplastic anemia as well as their therapeutic use to treat myeloproliferative neoplasms and viral infections, including SARS-CoV2. Understanding the opposing effects of interferons on hematopoiesis will elucidate immune responses and bone marrow failure syndromes, and future therapeutic approaches for patients undergoing HSC transplantation or fighting infectious diseases and cancer.

Fungal beta-glucans as adjuvants for treating cancer patients - A systematic review of clinical trials.

BACKGROUND & AIMS: Fungal ß-glucans have been considered as biological response modifiers (BRMs) promoting stimulation of immune system according to numerous scientific publications performed in vitro and in vivo. Some clinical trials involving such compounds started to be published since 1980's. This systematic review aimed to compile and compare clinical studies using these ß-glucans as adjuvants on patients undergoing cancer treatment. Healthy subjects and ß-glucans from other sources were excluded. METHODS: It was developed according to PRISMA-P guidelines (PROSPERO registered n. CRD42020151539), using PICO criteria and the following databases: PubMed, Scielo and LILACS. RESULTS: We found 1018 articles and after removing duplicated records, select by title/abstract and full-text, only 9 studies remained and 7 more were manually added, totalizing 16 trials involving 1650 patients, with arm sizes varying from 9 until 200 patients. The selected studies (published since 1992-2018) included subjects with diagnosis of 9 types of cancer. The studies used different sources of ß-glucans, such as yeast (Saccharomyces cerevisiae), mushrooms (Lentinula edodes and Schizophyllum commune) and non-described fungal sources. CONCLUSIONS: It was observed that the administration of ß-glucan is safe and well-tolerated. Most of the trials pointed that concomitant administration of ß-glucan with chemo or radiotherapy reduced the immune depression caused by such treatments and/or accelerated the recovery of white blood cells counts. However, some articles also commented that no statistical difference was encountered between ß-glucan treated vs. control groups, which gives a controversial conclusion about the ß-glucan effects. The great diversity among the methodology studies and insufficient information was an impeditive for achieving profound statistical analysis, therefore a narrative report of the included studies was performed indicating that further evidences are required to determine the efficacy of this adjuvant in the cancer treatment.

Preclinical Testing of Viral Therapeutic Efficacy in Pristane-Induced Lupus Nephritis and Diffuse Alveolar Hemorrhage Mouse Models.

Systemic lupus erythematosus (SLE) is a multifactorial and heterogeneous autoimmune disease involving multiple organ systems and tissues. Lupus nephritis occurs in approximately 60% of patients with SLE and is the leading cause of morbidity. Diffuse alveolar hemorrhage (DAH) is a rare but very serious complication of SLE with a greater than 50% associated mortality. The etiology of SLE is unclear but has proposed genetic, hormonal, and environmental aspects. Pristane is a saturated terpenoid alkane and has become the most popular laboratory model for inducing lupus in mice. The pristane model of SLE has the capacity to reproduce many components of the human presentation of the disease. Previous studies have demonstrated that virus-derived immune-modulating proteins have the potential to control inflammatory and autoimmune disorders. Serp-1, a 55 kDa secreted and highly glycosylated immune modulator derived from myxoma virus (MYXV), has potent immunomodulatory activity in models of vasculitis, viral sepsis, collagen-induced arthritis, and transplant rejection. This chapter describes the mouse preclinical pristane lupus model as a method to examine virus-derived protein efficacy for treating autoimmune diseases and specifically lupus nephritis and DAH.

An Immunomodulatory Gallotanin-Rich Fraction From Caesalpinia spinosa Enhances the Therapeutic Effect of Anti-PD-L1 in Melanoma.

PD-1/PD-L1 pathway plays a role in inhibiting immune response. Therapeutic antibodies aimed at blocking the PD-1/PD-L1 interaction have entered clinical development and have been approved for a variety of cancers. However, the clinical benefits are reduced to a group of patients. The research in combined therapies, which allow for a greater response, is strongly encouraging. We previously characterized a polyphenol-rich extract from Caesalpinia spinosa (P2Et) with antitumor activity in both melanoma and breast carcinoma, as well as immunomodulatory activity. We hypothesize that the combined treatment with P2Et and anti-PD-L1 can improve the antitumor response through an additive antitumor effect. We investigated the antitumor and immunomodulatory activity of P2Et and anti-PD-L1 combined therapy in B16-F10 melanoma and 4T1 breast carcinoma. We analyzed tumor growth, hematologic parameters, T cell counts, cytokine expression, and T cell cytotoxicity. In the melanoma model, combined P2Et and anti-PD-L1 therapy has the following effects: decrease in tumor size; increase in the number of activated CD4+ and CD8+ T cells; decrease in the number of suppressor myeloid cells; increase in PD-L1 expression; decrease in the frequency of CD8+ T cell expressing PD-1; improvement in the cytotoxic activity of T cells; and increase in the IFN γ secretion. In the breast cancer model, P2Et and PD-L1 alone or in combination show antitumor effect with no clear additive effect. This study shows that combined therapy of P2Et and anti-PD-L1 can improve antitumor response in a melanoma model by activating the immune response and neutralizing immunosuppressive mechanisms.

Omega-3 fatty acids in the psychological and physiological resilience against COVID-19.

As the infected cases of COVID-19 reach more than 20 million with more than 778,000 deaths globally, an increase in psychiatric disorders including anxiety and depression has been reported. Scientists globally have been searching for novel therapies and vaccines to fight against COVID-19. Improving innate immunity has been suggested to block progression of COVID-19 at early stages, while omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have immunomodulation effects. Moreover, n-3 PUFAs have also been shown to improve mood disorders, thus, future research is warranted to test if n-3 PUFAs may have the potential to improve our immunity to counteract both physical and mental impact of COVID-19.

The key role of zinc in elderly immunity: A possible approach in the COVID-19 crisis.

BACKGROUND & AIMS: The COVID-19 infection can lead to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly affecting patients aged 60 and older. Preliminary data suggest that the nutritional status can change the course of the infection, and on the matter, zinc is crucial for growth, development, and the maintenance of immune function. In the absence of treatment for this virus, there is an urgent need to find alternative methods that can contribute to control of disease. The aim of this paper is to establish the relation between zinc and COVID-19. METHODS AND RESULTS: From the prior scientific knowledge, we have performed a review of the literature and examine the role of zinc in immune function in the infection by COVID-19. Our findings are that the zinc as an anti-inflammatory agent may help to optimize immune function and reduce the risk of infection. CONCLUSIONS: Zinc supplementation can be a useful strategy to reduce the global burden of infection in the elderly, there is a need the increased reporting to improve our understanding of COVID-19 and the care of affected patients.

Associations between hypovitaminosis D and COVID-19: a narrative review.

In the search for factors affecting incidence and lethality of the current COVID-19 pandemic, recent association studies explored the possible role of vitamin D deficiency. Altogether, these studies, in most cases based on cross-sectional analyses, could not yet provide a convincing demonstration of a cause-effect relationship. In this editorial, the authors describe the scientific evidence underlying a possible role of vitamin D in the prevention and development of the pandemic, considering its immunomodulatory role and antiviral effects. They conclude that further studies are needed to (1) better explore possible associations between vitamin D deficiency and COVID-19 morbidity and lethality, and (2) assess if compensating such deficiency could avoid or mitigate the worst manifestations of COVID-19. They highlight the need for public health campaigns to promote consumption of vitamin D-rich foods and proper sunlight exposition or, when this is not possible, controlled pharmaceutical supplementation, especially in countries with high prevalence of hypovitaminosis D.

Inducing inflammatory response in RAW264.7 and NK-92 cells by an arabinogalactan isolated from Ferula gummosa via NF-κB and MAPK signaling pathways.

The polysaccharide isolated from F. gummosa (FGP) was found homogenous with a weight average molecular weight (Mw) of 50.0 × 103 g/mol and radius of gyration (Rg) of 105.3 nm. The FGP was an arabinogalactan with a backbone formed of →6)-ß-Galp-1→ residues having random branching points at C-3 extended with either ß-Galp-(1→3)-ß-Galp-(1→ or α-Araf-(1→ side chain residues. FGP exhibited proliferative effect on RAW264.7 cells and induced macrophages to exert proinflammatory response releasing NO and up-regulating the transcription of cytokines including TNF-α, IL-1ß, IL-6 and IL-12. The FGP induced NK-92 cells to up-regulate the expressions of TNF-α, IFN-γ, granzyme-B, perforin, NKG2D and FasL. The presence of p-NF- κB, p-ERK, p-JNK and p-p38 in RAW264.7 and NK-92 cells indicated their activation through NF-κB and MAPKs signaling pathways. These findings suggested that polysaccharides from F. gummosa are potent in boosting immune system and thus may be considered for further studies of biomedical applications.

Fructo-Oligosaccharides Modify Human DC Maturation and Peanut-Induced Autologous T-Cell Response of Allergic Patients In Vitro.

Background: Dendritic cells (DCs) play an important role in antigen presentation, and are an interesting target for immune-modulation in allergies. Short- and long-chain fructo-oligosaccharides (scFOS/lcFOS, FF) have immunomodulatory capacities, and may influence the outcome of DC antigen presentation. Objective: This study investigated the effect of FF during DC maturation and allergen presentation using cells of peanut-allergic patients in an autologous DC-T cell assay. Methods: CD14+ and CD4+ T cells were isolated from peanut-allergic patients. CD14+ monocytes were differentiated into immature DCs (imDCs), and matured (matDCs) in the presence or absence of crude peanut-extract (CPE) and/or FF, and co-cultured in an autologous DC-T cell assay. T cell polarization, proliferation and cytokine production were measured. Results: Expression of maturation surface molecule markers on matDCs was not affected by CPE and/or FF. By contrast, the IL-10 secretion by matDCs increased compared to imDCs, upon exposure to CPE and FF compared to CPE alone. Also the IP-10 secretion increased in CPE/FF-matDCs compared to imDC. CPE-matDCs enhanced IL-13 release in the DC-T-cell assay and Treg polarization in presence or absence of FF. CPE/FF-DCs tended to increase the Treg/Th1 and Treg/Th2 ratios compared to matDCs. The proliferation of both Treg and Th2 cells tended to increase when T cells were co-cultured with CPE-matDCs compared to matDCs, which became significant when CPE-matDCs were also exposed to FF and a same tendency was shown for Th1 proliferation. Conclusion: Only in the presence of FF, CPE-matDCs produced increased regulatory and Th1-related mediators. CPE-matDCs modified T cell polarization and proliferation, and additional exposure to FF tended to enhance Treg/Th2 and Treg/Th1 ratios instructed by CPE/FF-matDCs. However this effect was not strong enough to suppress CPE-matDCs induced IL-13 release by Th-cells. This indicates the ability of FF to modify DC maturation in the presence of an allergen supporting a more Treg/Th1 prone direction of the successive allergen specific Th2 cell response.

Exploring the Evidence for an Immunomodulatory Role of Vitamin D in Juvenile and Adult Rheumatic Disease.

Vitamin D is synthesized in the skin following exposure to UVB radiation or is directly absorbed from the diet. Following hydroxylation in the liver and kidneys, vitamin D becomes its bioactive form, 1,25(OH)2D, which has been described to have potent immunomodulatory capacity. This review will focus on the effect of vitamin D in modulating the dysregulated immune system of autoimmune rheumatic diseases (ARD) patients across age, in particular in arthritis (rheumatoid arthritis and juvenile idiopathic arthritis), and systemic lupus erythematosus (with adult and juvenile onset). As well as delineating the impact of vitamin D on the innate and adaptive immune functions associated with each disease pathology, this review will also summarize and evaluate studies that link vitamin D status with disease prevalence, and supplementation studies that examine the potential benefits of vitamin D on disease outcomes. Exploring this evidence reveals that better designed randomized controlled studies are required to clarify the impact of vitamin D supplementation on ARD outcomes and general health. Considering the accessibility and affordability of vitamin D as a therapeutic option, there is a major unmet need for evidence-based treatment recommendations for the use of vitamin D in this patient population.

Avaliação da suplementação diária de ácidos graxos poli-insaturados de ômega-3 e aspirina em baixa dosagem no tratamento de periodontite agressiva generalizada: estudos clínicos controlados randomizados / Evaluation of omega-3 polyunsaturated fatty acids daily supplementation plus low-dose aspirin to treat generalized aggressive periodontitis: randomized controlled clinical trials

A destruição periodontal resulta principalmente da resposta inflamatória exacerbada do hospedeiro frente ao desafio bacteriano. Por isso, pesquisas envolvendo a modulação da resposta do hospedeiro têm sido desenvolvidas com o objetivo de facilitar a resolução da inflamação, bem como promover reparação tecidual e estabilidade periodontal. Recentemente, o uso de ácidos graxos poli-insaturados de ômega-3 (AGP Ω-3) e ácido acetilsalicílico (AAS) foi relacionado à produção de mediadores lipídicos mais bioativos e à melhores resultados clínicos no tratamento de periodontite crônica. Desse modo, pesquisas envolvendo modulação das respostas inflamatórias de portadores de periodontite agressiva (PAg) podem ser de grande valia. Assim, o objetivo dos presentes estudos clínicos controlados randomizados foi avaliar a utilização da suplementação de 900 mg AGP Ω-3 e 100 mg de AAS por 180 dias como adjuvantes ao tratamento de PAg generalizada (PAgG). (1) Selecionou-se 38 pacientes com PAgG os quais receberam debridamento subgengival associado a AGP Ω-3 e AAS (n=19) ou placebo (n=19). Ambos os grupos apresentaram diminuição (p<0,05) em todos os parâmetros clínicos avaliados, bem como em IL-1ß, sem diferença entre os tratamentos (p>0,05). O nível de TIMP-2 diminuiu significantemente no grupo controle, porém se manteve estável no grupo teste. Concluiu-se que a nova terapia proposta não trouxe benefícios clínicos no tratamento não-cirúrgico de PAgG. (2) Selecionou-se 34 pacientes com PAgG previamente submetidos à terapia básica que apresentavam bolsas residuais e foram submetidos à cirurgia de acesso para raspagem e alisamento radicular associado a AGP Ω-3 e AAS (n=17) ou placebo (n=17). Após 6 meses, ambos os grupos obtiveram diminuição na PS (p<0,05), porém somente o grupo teste obteve ganho no NIC na comparação intergrupo (p=0,02), assim como apresentou menor recessão gengival (p=0,03), diminuição da hipersensibilidade dentinária (p=0,01), menor consumo de analgésicos (p=0,02) e diminuição intragrupo de IL-10 (p<0,05). Concluiu-se que a nova terapia proposta trouxe benefícios clínicos no tratamento de bolsas residuais de pacientes com PAgG(AU)

Periodontal destruction results mainly from the exacerbated host inflammatory response to the bacterial challenge. For this reason, research involving the modulation of host response has been developed aiming to facilitate the resolution of inflammation, as well as to promote tissue repair and periodontal stability. Recently, the use of omega-3 polyunsaturated fatty acids (Ω-3 PUFA) and low-dose acetylsalicylic acid (ASA) was related to the production of enhanced lipidic mediators and to better clinical outcomes in the treatment of chronic periodontitis. Thus, the aim of the present randomized controlled clinical trials was to evaluate the use of 900 mg Ω-3PUFA and 100 mg ASA for 180 days as adjuvants to the treatment of generalized aggressive periodontitis (GAgP). (1) Thirty-eight GAgP patients were submitted to subgingival debridement associated with Ω-3 PUFA and ASA (n=19) or placebo (n=19). Both groups showed a statistically significant decrease (p<0.05) in all clinical parameters, as well as a decrease in IL-1ß, with no difference between treatments (p>0.05). The TIMP-2 level significantly decreased in the control group and remained stable in the test group. It was concluded that the proposed new therapy did not bring clinical benefits in the non-surgical treatment (NST) of GAgP. (2) Thirty-four GAgP patients previously submitted to NST with residual pockets were selected and underwent open flap debridement associated with Ω-3 PUFA 3 and ASA (n=17) or placebo (n=17). After 6 months, both therapies led to decreased PD (p>0.05), but only the test group had CAL gain in the intergroup comparison (p=0,02), as well as presented less gingival recession (p=0,03), decreased dentin hypersensitivity (p=0,01), lower consumption of analgesics (p=0,02) and significant intragroup reduction of IL-10 (p<0.05). It was concluded that the proposed new therapy brought clinical benefits in the surgical treatment of GAgP patient(AU)

An immunomodulatory feed additive enhances in vitro viral vaccine recall antigen responses in dairy heifers.

Enhancing immunological responses to vaccination is an important goal in many herd health management systems. OmniGen-AF®(OG) is an immunomodulatory feed additive that has been shown to enhance innate immune function in ruminants and its effects on adaptive immunity require additional study. The objective of this study was to evaluate post-vaccine antibody titers and circulating cellular memory development in heifers fed OG and administered a commercially available modified-live bovine respiratory disease (BRD) vaccine. Twenty-four Holstein heifers were assigned to one of two diets for 170 days: Control TMR (CON; n = 11), or TMR plus OG (TRT; 9 g/100 kg BW/day; n = 13). Samples for hematology, serology, and cellular assays were collected on D-110, 0, 21, 42, and 60 of the trial. Heifers were administered two priming doses of a modified-live BRD vaccine, with a third dose given on D0. There were no significant differences in total WBC and absolute number or the percentage of circulating lymphocytes, monocytes, neutrophils, RBC, or platelets on D-110 through D21. On D42 and D60, CON had significantly higher numbers of lymphocytes. On D0, mean serum neutralizing (SN) titer to BHV-1 was significantly higher for CON compared to TRT. SN titers were not significantly different between CON and TRT at any other time point for BHV-1, BVDV type 1, or BVDV type 2. TRT mounted a significantly stronger recall proliferative response to 0.5 multiplicity of infection (MOI) of BHV-1, BVDV type 1 and BVDV type 2 on D42 and D60; 0.25 MOI of BVDV type 1 on D21 and D42; and 0.25 MOI BVDV type 2 on D42 compared to CON. IL-4 production induced by 0.5 and 1.0 MOI BHV-1 (D42 and D60); 0.25 MOI of BVDV type 1 (D21); and 0.25 and 0.5 MOI of BVDV type 2 (D60) were significantly higher for TRT than CON. IL-17 production induced by 0.25 MOI of BVDV type 1 was significantly higher on D60 for TRT compared to CON. IFN-gamma and IL-10 were not significantly different between treatments. These data indicate feeding OG has a beneficial effect on responses to vaccine antigens in Holstein dairy heifers.

Establishment of enzyme-linked immunosorbent facilitated antigen binding as a biomarker assay for Japanese cedar pollen allergy immunotherapy.

BACKGROUND: Clinical efficacy of allergen-specific Immunotherapy (AIT) towards Japanese cedar (JC) pollen allergy is firmly established but JC pollen-specific biomarker assays are lacking. Treatment-related increase of allergen-specific antibodies is a robust biomarker of successful AIT. Allergen-specific non-IgE antibodies are believed to reduce the effects of allergen exposure by competing with IgE for allergen binding, and in-vitro assays quantifying the effects of AIT-induced IgE-blocking antibodies are advantageous. A cell-free enzyme-linked immunosorbent facilitated antigen binding (ELIFAB) assay of JC pollen was established. METHODS: Serum IgE-allergen complexes were captured by immobilized recombinant CD23, and allergen-IgE-CD23 complexes were detected by a biotin-conjugated anti-human IgE antibody. Sera from JC pollen-allergic subjects without or with subcutaneous immunotherapy (SCIT) with JC pollen extract were used (n = 11/group). RESULTS: Optimal assay conditions were established at 20 µg/mL CD23 and 0.3 µg/mL JC pollen extract, and the dependency on CD23 and IgE was verified. The data show that the JC pollen ELIFAB assay is fit for purpose and demonstrates that the IgE-blocking activity is significantly increased in the JC pollen SCIT group compared with the non-treated group. CONCLUSION: The JC pollen ELIFAB assay represents a simple, cell-free biomarker assay for monitoring the development of IgE-blocking antibody activity during JC pollen AIT.

Molecular properties and immunomodulatory activities of a water-soluble heteropolysaccharide isolated from Plantago asiatica L. leaves.

This study aims at investigating physical-chemical properties of a water-soluble heteropolysaccharide from Plnatago asiatica L. leaves, and its immunomodulatory effects on macrophages RAW264.7 cells. Hot water-extracted crude polysaccharide from the plant leaves (PLLCP) was fractionated into four fractions by DEAE Sepharose Fast Flow eluted with 0.1-0.5 M NaCl solutions. The most abundant fraction (0.3 M NaCl elution), designated PLLP-2, was identified as a heteropolysaccharide with an average molecular weight (Mw) of 3.54 × 104 and composed mainly of Gal (34.4%), GalA (36.5%), Ara (10.1%) and Rha (8.4%). PLLP-2 was an acidic polysaccharide exhibiting inflaky curly aggregation with smooth surface. PLLCP and its main subfraction PLLP-2 displayed immunomodulatory activities by stimulating the production of pro-inflammatory cytokines, including TNF-α and IL-1ß in macrophage RAW264.7 cells. These results indicate that the main polysaccharide fraction purified from P. asiatica L. leaves is probably pectin, and have potential immunomodulatory function.

The core structure characterization and of ginseng neutral polysaccharide with the immune-enhancing activity.

The study aims to clarify the structural domain required for the immune enhancement of ginseng neutral polysaccharide (GPN). GPN was first obtained through water extraction and ion-exchange chromatography from Panax ginseng. GPN was hydrolyzed by α-amylase for 24 h and fractionated through gel permeation chromatography to give two final fragments GPNE-I and GPNE-II, with molecular weight of 8.03 × 104 Da for GPNE-I and 3.15 × 104 Da for respectively. FT-IR, methylation and 1D/2D NMR analysis demonstrated that GPNE-I was a heteropolysaccharide consisting mainly of a glucan domain and type I and II arabinogalactans (AG-I and AG-II). GPNE II was a glucan consisting of (1 → 4)-α-d-Glcp backbone with a substitution at O-6 on every two residues. (1 → 3)-α-d-Glcp and (1 → 6)-α-d-Glcp were located at the branches. In the two fractions, both α- and ß-t-Glcp as reductive terminals and →4)-α-Glcp as a non-reducing end were detected. The branching degrees of GPNE-I and GPNE-II were 38.17% and 50.78%, respectively. Immunological experiments revealed that GPNE-I exhibited more effectively stimulated lymphocyte proliferation than GPN and GPNE-II, indicating the former showed potential for immunomodulators applications, indicating that GPNE-I might be the core active domain and necessary for GPN to promote lymphocyte proliferation.