Effect of splenic transfer factor on the development of intestinal mucosal barrier in laying hens.

BACKGROUND: The aim of this study was to investigate the effects of different doses of chicken spleen transfer factor (TF) on the structure of intestinal epithelial cells in different age groups. One-day-old White Leghorns laying hens were randomly divided into four groups: three groups were administered TF at different dosages (0.10, 0.25 or 1.00 mL) and a fourth group was set as control (administered saline, 1.00 mL). Using hematoxylin and eosin staining, high-throughput sequencing, microbiota analysis, quantitative polymerase reaction and western blotting. RESULTS: We measured the effects of different doses of TF on the following: intestinal mucosal epithelial tissue morphology, intestinal mucosal epithelial barrier-related gene expression profiles, and intestinal epithelial tight junction gene protein levels. The collected data show that TF can improve the absorption of nutrients by increasing villus height and crypt depth, and regulate intestinal flora disorders. Furthermore, we verified that the expression of the claudin and occludin tight junctions between intestinal epithelial cells was increased with TF. this research is very important for focusing on the structure and gene expression of intestinal tissues. CONCLUSION: The results provide a scientific rationale for feeding and nutrition programs for green and healthy farming, as well as technical support to improve the production efficiency of the livestock and poultry breeding industry. © 2022 Society of Chemical Industry.

Effects of Cd uptake, translocation and redistribution in different hybrid rice varieties on grain Cd concentration.

In order to identify the key transport process that determines the Cd concentration in brown rice, this study used 21 hybrid rice varieties as experimental materials and conducted field experiments in Qiyang (cadmium-contaminated site) and Yongding (low-cadmium site). Cd concentrations in 8 organs were measured, and bioconcentration factors and transfer factor were further calculated. The results showed that the Cd concentrations of the organs related to the xylem transport were as follows: root > node > stem > leaf sheath > leaf. In the phloem, the Cd concentrations were as follows: rachis > brown rice > rice husk. And the results of the correlation analysis found that Cd concentration between brown rice and root showed a significant positive correlation in Cd-contaminated site, but no significant correlation in low-cadmium site. Meanwhile, at both experimental sites, the Cd concentration of brown rice showed the most significant correlation with the phloem transfer factor from leaf and leaf sheath to brown rice. Principal Component Analysis (PCA) and stepwise regression analysis likewise found that Cd concentration in leaf and leaf sheath and their phloem transport of Cd to brown rice were significantly and positively correlated with Cd concentration in brown rice. The above results showed that the transport of leaf and leaf sheath to brown rice was a key process, and played a more important role in the accumulation of cadmium in brown rice than in root.

The bovine dialysable leukocyte extract IMMUNEPOTENT CRP induces immunogenic cell death in breast cancer cells leading to long-term antitumour memory.

BACKGROUND: Cancer recurrence is a serious problem in breast cancer (BC) patients, and immunogenic cell death (ICD) has been proposed as a strategy to overcome this recurrence. IMMUNEPOTENT CRP (ICRP) acts as an immunomodulator and can be cytotoxic to cancer cells. Thus, we evaluated if ICRP induces ICD in BC cells. METHODS: Immunogenicity of ICRP-induced cell death was evaluated in vitro, analysing the principal biochemical characteristics of ICD in MCF-7, MDA-MB-231 and 4T1 cells. Ex vivo, we assessed the ability of killed cancer cells (KCC) obtained from ICRP-treated 4T1 cells (ICRP-KCC) to induce DC maturation, T-cell priming and T-cell-mediated cancer cytotoxicity. In vivo, we evaluated tumour establishment and antitumour immune memory after prophylactic ICRP-KCC vaccination in BALB/c mice. RESULTS: ICRP induced caspase-independent, ROS-dependent cell death, autophagosome formation, P-eIF2α, chaperone protein exposure, CD47 loss, ATP and HMBG1 release in BC cells. Additionally, ICRP-KCC promoted DC maturation, which triggered T-cell priming and cancer cytotoxicity. Prophylactic vaccination with ICRP-KCC prevented tumour establishment and induced long-term antitumour memory in BALB/c mice, involving DC maturation in lymph nodes, CD8+ T-cell augmentation in lymph nodes, peripheral blood and tumour site and ex vivo tumour-specific cytotoxicity by splenocytes. CONCLUSIONS: ICRP induces ICD in BC cells, leading to long-term antitumour memory.

Serum Derived Transfer Factor Stimulates the Innate Immune System to Improve Survival Traits in High Risk Pathogen Scenarios.

Preclinical Research Transfer Factors (TFs) are low molecular weight (<5,000 daltons) biological response mediators. In the present study, a serum derived TF improved the ability of the recipient animal to survive high-risk infectious challenges (salmonellosis and canine parvoviral enteritis (CPV)) by altering the host's cytokine response profile. Mice mortally challenged with 5,000 colony-forming units of Salmonella experienced a group mortality of 73% while mice treated with a single 5 mg dose of the TF demonstrated a significant decrease in morbidity (7%, p ≤ 0.01). The splenic bacterial load in untreated mice was over 10,000 times higher than that in the TF treated mice. Twenty-four hours post-administration, the treated murine population expressed a rapid temporal increase in serum IL-6 (26-fold) and INF-γ (77-fold) concentrations. IL-6 can act as a critical signal regulating action against bacterial pathogens. A comparative double-blind study performed using dogs confirmed to be undergoing a canine parvovirus challenge showed that when conventional supportive therapy was supplemented with a single 5 mg TF dose there was a reduction (p ≤ 0.01) in group mortality (68% of the TF treated group survived versus 32% of the placebo group), an observation consistent with the observed increase in INF-γ, a cytokine associated with promoting antiviral activity. Drug Dev Res 78 : 189-195, 2017. © 2017 Wiley Periodicals, Inc.

Anti-inflammatory effect of dialysable leucocyte extract in a rat model of osteoarthritis: histopathological and molecular characterization.

OBJECTIVES: To evaluate the effect of dialysable leucocyte extract (DLE) on pro- and anti-inflammatory profiles in a rat model of osteoarthritis (OA). METHOD: Forty-eight male Wistar rats were divided into three groups: normal rats without treatment, OA rats treated with placebo, and OA rats treated with DLE. After treatment, the animals were killed to obtain cartilage for histological analysis and to determine the expression of pro- and anti-inflammatory cytokines by reverse transcription multiplex polymerase chain reaction (RT-MPCR) and immunohistofluorescence analyses. RESULTS: Histological analysis revealed that OA cartilage from rats treated with DLE displayed similar characteristics to non-OA cartilage from the control group. The OA cartilage treated with placebo showed alterations in the cellular architecture and in chondrocyte cluster formation. Analysis of cytokine expression by RT-MPCR showed that OA cartilage from DLE-treated rats expressed platelet-derived growth factor (PDGF), interferon (IFN)-γ, and fibroblast growth factor (FGF)-2, similar to non-OA cartilage from the control group. However, OA cartilage from rats treated with placebo expressed interleukin (IL)-1, PDGF, and I kappa B (IκB). Confocal immunodetection of FGF-2, PDGF, and non-phosphorylated IκB showed that they were distributed in the cytoplasm of most chondrocytes in OA cartilage from DLE-treated rats whereas no nuclear factor kappa B (NF-κB) expression was observed in the nuclei. Instead, in OA cartilage from the placebo group, only weak FGF-2 staining was observed, PDGF and IκB were not detected, and NF-κB was strongly observed in both cytoplasm and nuclei. CONCLUSIONS: Our findings suggest that DLE treatment modifies the OA process, promoting the expression of anti-inflammatory cytokines and diminishing the inflammatory effects, avoiding the nuclear translocation of NF-κB in chondrocytes.

A low-molecular-weight dialysable leukocyte extract selectively enhances development of CD4⁺RORγt⁺ T cells and IL-17 production.

A low-molecular-weight (under 10 kDa) dialysable leukocyte extract (called transfer factor, TF) has been shown to be a prospective substance to improve or modulate immune response in autoimmunity, inflammation, infectious diseases or cancers. However, the use of TF has been limited by the absence of any data on the mechanism of its action. Here we show that TF prepared from peripheral blood leukocytes of healthy human donors displays multiple regulatory effects on individual parameters of the immune system. TF decreases proliferation of T and B lymphocytes and partially alters the production of cytokines and nitric oxide by activated macrophages. TF also inhibits production of T helper 1 (Th1) cytokines interleukin 2 (IL-2) and interferon γ, slightly stimulates production of Th2 cytokine IL-10 and considerably enhances the secretion of IL-17 by activated mouse spleen T cells. At the molecular level, TF enhances expression of genes for transcription factor RORγt and for IL-17. The enhanced expression of the RORgt gene corresponds with an increase in the number of RORγt⁺CD4⁺ Th17 cells and with enhanced IL-17 production. In contrast, the expression of the Foxp3 gene and the proportion of CD4⁺CD25⁺Foxp3⁺ regulatory T cells are not significantly changed in the presence of TF. These results suggest that the activation of pro-inflammatory Th17 cells, which have multiple immunoregulatory properties, could be the main mechanism of the immunomodulatory action of a low-molecular-weight leukocyte extract.

Response of Amaranthus tricolor to cesium stress in hydroponic system: Growth, photosynthesis and cesium accumulation.

Remediation of the cesium-contaminated environment is of paramount importance, and phytoremediation is a cost-effective and green technique. In this paper, the response of Amaranthus tricolor to cesium ions in hydroponic solution was investigated at various cesium concentration (0, 0.05, 0.2, 0.4 and 0.6 mM), in terms of the growth weight, height and photosynthesis. The maximal Cs content in stems and leaves of A. tricolor was 13.05 mg/g dry wt under spiked Cs level of 0.4 mM in solution. The maximal transfer factor (TF) and bioconcentration factor (BCF) were 1.87 and 181.25 respectively, when the corresponding Cs content in roots and shoots was 7.04 mg/g and 13.05 mg/g dry wt respectively. TFs are higher than 1 in the conditions of normal plant growth. The growth of A. tricolor was enhanced after the treatment of Cs at low concentrations (0.05 and 0.2 mM), while it was inhibited at 0.4 and 0.6 mM. The leaf number and dry weight of stem, leaf parts and root parts were maximum at the spiked cesium level of 0.2 mM, which significantly increased by 19.19%, 47.56% and 94.56% respectively, compared with the control samples. Under 0.6 mM cesium stress, curl and withering of the leaves occurred, and the plant growth and cesium accumulation dropped to the minimum. Cs at the spiked level of 0.6 mM in solution inhibited the performance of PSII, especially in terms of blockage in electron transfer process beyond QA and restraint of P700 reduction. On contrast, the performance of PSII was enhanced by the spiked Cs at level of 0.2 mM, leading to the growing density of reaction centers per excited cross-section and increasing electron transfer process beyond QA. In summary, A. tricolor has potential for remediating the Cs-contaminated environment.

The combined impacts of selenium and phosphorus on the fate of arsenic in rice seedlings (Oryza sativa L.).

Although the single role of selenium (Se) or phosphorus (P) in regulating the As contamination of rice plants has been reported in some studies, the combined impacts of Se and P on the fate of As and the underlying mechanisms are poorly understood. To address this knowledge gap, the uptake, translocation, and biotransformation of As mediated by Se were investigated in rice (Oryza sativa L.) seedlings hydroponically cultured with P-normal and P-deficient conditions. The results showed Se addition stimulated the uptake of arsenite and arsenate by 15.6% and 30.7%, respectively in P-normal condition, and such effect was more profound in P-deficient condition with the value of 43.8% and 70.8%. However, regardless of Se addition, P-deficiency elevated the As uptake by 47.0%-92.1% for arsenate but had no obvious effects for arsenite. Accompanying with the As transfer factorShoot/Root reduced by 74.5%-80.2% and 71.1%-85.7%, Se addition decreased the shoot As content by 65.8%-69.7% and 59.6%-73.1%, respectively, in the arsenite- and arsenate-treated rice plants. Relative to the corresponding treatments of P-normal condition, P-deficiency reduced the As transfer factorShoot/Root by 38.9%-52.5% and thus decreasing the shoot As content by 35.2%-42.5% in the arsenite-treated plants; while the opposite impacts were observed in the arsenate-treated plants, in which the shoot As content was increased by 22.4%-83.7%. The analysis results of As species showed As(III) was dominant in both shoots (68.9%-75.1%) and roots (94.9%-97.2%), and neither Se addition nor P-deficiency had obvious impacts on the interconversion between As(III) and As(V). Our results demonstrate the regulating roles of Se in As accumulation mainly depend on P regimes and the specific rice tissues, but the effects of P-deficiency on the fate of As were influenced by the form of As added to the culture.

[Potential of prevention of metastasizing with the aid of tumor-specific transfer-factor].

The report discusses our experimental data in support of biotherapy which uses chemotherapy and antitumor immune treatment with in vivo xenogenic transfer-factor polypeptides (TFP) isolated from lymphocytes sensitized to antigens of given tumor. After excision of primary tumor--lung carcinoma of Lewis--mice C57BL/6 were injected intraperitoneally with xenogenic TFP (200 pg/body, twice) and a cytostaic dose of cyclophosphamide. Such adjuvant chemotherapy was found to prevent metastases from spreading to the lung in 100%. The marked anti-metastatic effect of the treatment correlated with recovery of splenic cell mass and its cellular structure, higher levels of large granular lymphocytes in peripheral blood and enhanced functional activity of cytotoxic cells in vitro. Our results point to a possibility of raising efficacy of treating solid malignancies with adjuvant chemotherapy in combination with adoptive immune therapy.

Requirement of precommitted cells as targets for the augmentation of lymphocyte proliferation by leukocyte dialysates.

After our initial report tha leukocyte dialysates containing transfer factor augment the thymidine incorporation of antigen-stimulated lymphocytes, we have adapted the system to microleukocyte cultures. This modification permits both (a) the simultaneous assay of a single dialysate on the cells of multiple individuals, and (b) the assay of multiple dialysates on the cells of a single individual. The data thus secured, demonstrate that dialysates from both skin-test-positive and -negative donors produced similar degrees of augmentation whether the data are expressed as an arithmetic difference or as a ratio. When expressed as an arithmetic difference, the amount of augmentation is increased in proportion to the level of thymidine incorporation of the assay cells when they were stimulated by antigen alone. When expressed as a ratio, however, the degree of augmentation is independent of the response of the assay cells. An analysis of the ability of dialysates to engage previously uncommitted lymphocytes and thus to augment thymidine incorporation, revealed that precommitted cells were required. In these experiments, antigen-reactive cells were deleted from populations of peripheral blood lymphocytes by incubation with purified protein derivative of tuberculin, diphtheria toxoid, or streptokinase-streptodornase in the presence of [3H]thymidine of high specific activity. This deletion depressed or abolished the effect of dialysate on the residual population when it was recultured with the same antigen, but the effect on the response of the remaining lymphocytes to other antigens was unaltered. In this study, leukocyte dialysate appeared to augment nonspecifically the thymidine incorporation of an antigen-specific precommitted clone of lymphocytes. The relationship of these adjuvant effects on peripheral blood lymphocytes in vitro to the specific and nonspecific activities of transfer factor in vivo remains to be elucidated.

Antiangiogenic and antitumor effects of IMMUNEPOTENT CRP in murine melanoma.

BACKGROUND: Skin cancers are common, and there has recently been a dramatic increase in their incidence, particularly in the occurrence of melanoma. Furthermore, relapse after curative surgical treatment of melanoma remains a significant clinical challenge and accounts for most of the mortality of this disease. OBJECTIVE: The aim of this study was to determine whether IMMUNEPOTENT CRP affects B16F10 melanoma cells and tumors growth and vascular endothelial growth factor (VEGF) production in vivo and in vitro. METHODS: B16F10 cells and B16F10-inoculated mice were treated with different concentrations of IMMUNEPOTENT CRP. Outcomes were then evaluated using MTT, TUNEL, Caspase-3, senescence, ELISA and colorimetric assays. Parameters related to survival and tumor weight were also assessed. RESULTS: IMMUNEPOTENT CRP decreased the viability of B16F10 cells by increasing apoptosis of the treated cells, and VEGF production was decreased both in vitro and in vivo. Furthermore, treatment prevented metastasis, delayed the appearance of tumors, decreased tumor weight and improved the survival of tumor-bearing mice. DISCUSSION: These observations suggest that IMMUNEPOTENT CRP can be used to suppress growth and metastasis by using targeting proteins such as VEGF.

CD80 Expression Correlates with IL-6 Production in THP-1-Like Macrophages Costimulated with LPS and Dialyzable Leukocyte Extract (Transferon®).

Transferon® is a complex drug based on a mixture of low molecular weight peptides. This biotherapeutic is employed as a coadjuvant in clinical trials of several diseases, including viral infections and allergies. Given that macrophages play key roles in pathogen recognition, phagocytosis, processing, and antigen presentation, we evaluated the effect of Transferon® on phenotype and function of macrophage-like cells derived from THP-1 monocytes. We determined the surface expression of CD80 and CD86 by flow cytometry and IL-1ß, TNF-α, and IL-6 levels by ELISA. Transferon® alone did not alter the steady state of PMA-differentiated macrophage-like THP-1 cells. On the contrary, simultaneous stimulation of cells with Transferon® and LPS elicited a significant increase in CD80 (P ≤ 0.001) and CD86 (P ≤ 0.001) expression, as well as in IL-6 production (P ≤ 0.05) compared to the LPS control. CD80 expression and IL-6 production exhibited a positive correlation (r = 0.6, P ≤ 0.05) in cells exposed to Transferon® and LPS. Our results suggest that the administration of Transferon® induces the expression of costimulatory molecules and the secretion of cytokines in LPS-activated macrophages. Further studies are necessary to determine the implication of these findings in the therapeutic properties of Transferon®.

Bovine dialyzable leukocyte extract modulates AP-1 DNA-binding activity and nuclear transcription factor expression in MCF-7 breast cancer cells.

BACKGROUND: We have previously demonstrated that bovine dialyzable leukocyte extract (bDLE) induces death through an apoptosis mechanism in MCF-7 breast cancer cells. Depending on the cell type and stimulus, activating protein-1 (AP-1) has been shown to regulate cell proliferation and differentiation, the stress response, apoptosis and survival. It remains unknown whether AP-1 and other transcription factors are mechanisms by which bDLE induces cell death. METHODS: To determine whether bDLE modulates the AP-1 DNA binding and gene expression, MCF-7 breast cancer cells were treated with bDLE (0, 1, 5, 10 U) for 72 h and evaluated by electrophoretic mobility shift assay, reverse transcriptase-polymerase chain reaction and Western blot assays. RESULTS: bDLE induced inhibition of cell growth, suppressed the AP-1 DNA-binding activity, decreased c-Jun protein expression and modulated NFATx, NFATc, NFkappaB, c-Jun and c-Fos transcription factor gene expression in MCF-7 breast cancer cells. DISCUSSION: The present data indicate that bDLE can block the AP-1 DNA-binding activity and expression of several transcriptions factors in breast cancer cells, which will have great potential in improving cancer therapy.

The dialyzable leukocyte extract TransferonTM inhibits tumor growth and brain metastasis in a murine model of prostate cancer.

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide. Dialyzed Leukocyte Extracts (DLEs) are heterogeneous mixtures of low-molecular-weight peptides that improve clinical responses in various diseases. Here, we analyzed the effects of TransferonTM, a commercial DLE with characterized active pharmaceutical ingredient and proven batch-to-batch reproducibility, in preclinical models of PCa. We employed v-Src-transformed murine prostate epithelial (PEC-Src) cells, which recapitulate the transcriptional profiles in human PCa, can be grown in immunocompetent mice, and consistently form bone and brain metastases. In vitro, TransferonTM did not induce cytotoxicity nor alterations in migration /invasion of PEC-Src cells. In vivo, TransferonTM reduced metastatic dissemination after intracardiac injection of PEC-Src and inhibited tumor growth of subcutaneous isotransplants. The antineoplastic effect of TransferonTM correlated with changes in tumor infiltration, increased serum concentrations of IL-12 and CXCL1, and reduced levels of VEGF. Our results suggest that the antineoplastic effect produced by TransferonTM is due to its immunomodulatory activity and not by a direct effect on cancer cells, and indicate that TransferonTM could be beneficial as adjuvant therapy in PCa patients.

Stimulation of monocyte cGMP by leukocyte dialysates. An antigen-independent property of dialyzable transfer factor.

We studied the effects of dialysates from leukocyte lysates containing dialyzable transfer factor activity and other leukocyte dialysates devoid of transfer factor activity on accumulation of cyclic nucleotides in human leukocytes. Dialysates from normal leukocytes produced 4- to 11-fold increases in leukocyte cGMP, and experiments with purified cell populations revealed that the increases were predominantly, if not entirely, in blood monocytes. Substances that increased monocyte cGMP could be obtained from several cell populations including mononuclear cells from Hypaque-Ficoll gradients, plastic-adherent monocytes, nonadherent lymphocytes, and neutrophils, but were not present in dialysates of leukemic lymphocytes from patients with the Sezary syndrome. Moreover, dialysates that increased leukocyte cGMP had essentially no effect on intracellular cAMP. Dialysates of lysed mononuclear cells contained serotonin, ascorbate, and an unidentified cholinergic activity, agents known to increase leukocyte cGMP. After passage of dialyzable transfer factor from mononuclear cells through a gel-filtration column, four fractions were obtained that increased leukocyte cGMP. Two of these fractions contained ascorbate; two other active fractions, including one that also caused conversion of delayed skin tests, did not contain detectable ascorbate or serotonin. The dialysate of lysed neutrophils also increased cGMP, but this activity was limited to the column fractions which contained ascorbic acid. These observations raise the possibility that alterations in monocyte cGMP content could modulate either the specific antigen-dependent, or, more likely, the antigen-independent activities in preparations of transfer factor.

New and cost effective cell-based assay for Dialyzed Leukocyte Extract (DLE)-induced Jurkat cells proliferation under azathioprine treatment.

The human Dialyzed Leukocyte Extract (DLE) is a heterogeneous mix of oligopeptides of <10kDa, extracted from leukocytes of healthy donors. There is significant clinical evidence of improvement using DLE during treatment of allergies, cancer,immunodeficiencies, and in mycotic and viral infections. Nevertheless, the DLE exact nature and mechanism of action have been elusive for more than 50 years. DLE biological activity testing is necessary in DLE production and quality control. Both in vitro and in vivo assays exist: E-rosette test, induction of delayed type hypersensitivity in mice, leukocyte migration and IFN-γ secretion. The animal-origin materials and in vivo assays convey a considerable logistic, ethic and economic burden, meanwhile the available in vitro assays have been reported with limited reproducibility and sometimes contradictory results. Here we are reporting a new DLE biological activity cell-based assay. The A20 and Jurkat cell lines were treated with (+Aza) or without (-Aza) azathioprine, DLE (+DLE) or both (+Aza/+DLE). After 72h, the cell proliferation was analyzed by the MTT or BrdU incorporation assays. In +Aza/+DLE treated cells, we observed a significant higher proliferation, when compared with +Aza/-DLE. In the absence of Aza, cells did not present any proliferation difference between -DLE or +DLE treatments. Both assays, MTT and BrdU showed similar results, being the MTT test more cost effective and we select it for validation as DLE biological assay using Jurkat cells only. We tested three different lyophilized DLE batches and we found consistent results with acceptable assay reproducibility and linearity. The DLE capacity for rescuing Jurkat cell proliferation during +Aza treatment was consistent using different liquid and lyophilized DLE batches, presenting also consistent chromatographic profiles. Finally, DLE treatment in Jurkat cells did not result into significant IL-2 of IFN-γ secretion, and known lymphocyte proliferative drugs failed to rescue Jurkat cells viability in presence of +Aza, as +DLE treatment did in our MTT assay. In conclusion, our new cell-based MTT assay has excellent DLE biological activity consistency, robustness and is cost effective, presenting important advantages over previous DLE activity in vitro and in vivo assays.

Early Differentiation of Human CD11c+NK Cells with γδ T Cell Activation Properties Is Promoted by Dialyzable Leukocyte Extracts.

Reconstitution of the hematopoietic system during immune responses and immunological and neoplastic diseases or upon transplantation depends on the emergent differentiation of hematopoietic stem/progenitor cells within the bone marrow. Although in the last decade the use of dialyzable leukocyte extracts (DLE) as supportive therapy in both infectious and malignant settings has increased, its activity on the earliest stages of human hematopoietic development remains poorly understood. Here, we have examined the ability of DLE to promote replenishment of functional lymphoid lineages from CD34+ cells. Our findings suggest that DLE increases their differentiation toward a conspicuous CD56+CD16+CD11c+ NK-like cell population endowed with properties such as IFNy production, tumor cell cytotoxicity, and the capability of inducing γδ T lymphocyte proliferation. Of note, long-term coculture controlled systems showed the bystander effect of DLE-stromal cells by providing NK progenitors with signals to overproduce this cell subset. Thus, by direct effect on progenitor cells and through activation and remodeling of the supporting hematopoietic microenvironment, DLE may contribute a robust innate immune response by promoting the emerging lymphopoiesis of functional CD11c+ NK cells in a partially TLR-related manner. Unraveling the identity and mechanisms of the involved DLE components may be fundamental to advance the NK cell-based therapy field.

Transfer factor: a potential agent for cancer therapy.

This review has attempted to describe the characteristics of transfer factor which make it a very attractive potential agent for immunotherapy. Preliminary observations suggest that it may be capable of modifying resistance to a variety of diseases including cancer but considerable progress in basic knowledge regarding this agent is crucial to its successful application in clinical disease states. Fortunately, a sizable number of interested and dedicated investigators are exploring these difficult problems and their success may lead to new approaches in immunotherapy.

Bovine dialyzable leukocyte extract protects against LPS-induced, murine endotoxic shock.

The pathophysiology of endotoxic shock is characterized by the activation of multiple pro-inflammatory genes and their products which initiate the inflammatory process. Endotoxic shock is a serious condition with high mortality. Bovine dialyzable leukocyte extract (bDLE) is a dialyzate of a heterogeneous mixture of low molecular weight substances released from disintegrated leukocytes of the blood or lymphoid tissue obtained from homogenized bovine spleen. bDLE is clinically effective for a broad spectrum of diseases. To determine whether bDLE improves survival and modulates the expression of pro-inflammatory cytokine genes in LPS-induced, murine endotoxic shock, Balb/C mice were treated with bDLE (1 U) after pretreatment with LPS (17 mg/kg). The bDLE improved survival (90%), suppressed IL-10 and IL-6, and decreased IL-1beta, TNF-alpha, and IL-12p40 mRNA expression; and decreased the production of IL-10 (P<0.01), TNF-alpha (P<0.01), and IL-6 (P<0.01) in LPS-induced, murine endotoxic shock. Our results demonstrate that bDLE leads to improved survival in LPS-induced endotoxic shock in mice, modulating the pro-inflammatory cytokine gene expression, suggesting that bDLE is an effective therapeutic agent for inflammatory illnesses associated with an unbalanced expression of pro-inflammatory cytokine genes such as in endotoxic shock, rheumatic arthritis and other diseases.

Effect of transfer factor on tumor-associated immunity and tumor growth of the Dunning R-3327G rat prostate adenocarcinoma.

Of importance in the design and application of improved or new modalities of treatment are their evaluation on relevant animal models. In the case of prostate cancer (PCa) the Dunning R-3327 rat prostate adenocarcinoma (PCa), and its variant sublines, is one such experimental tumor model of its human counterpart. In a preliminary study, the effect of transfer factor (TF), one form of passive immunotherapy, on tumor-associated immunity (TAI) and tumour growth and histology of the G subline (a poorly differentiated, fast-growing, androgen sensitive, and poorly metastatic tumour of the Dunning R-3327 rat PCa) has been evaluated. TF prepared from the leukocytes of tumor-bearing animals and nontumor-bearing animals referred to as sensitized (STF) and unsensitized (UTF), respectively, had no significant effect on TAI or tumor size. The only noticeable effect of TF in this study was the presence of variable and moderate lymphocytic infiltrates, necrosis, and degenerative-type cells in tumors of animal recipients of STF. The failure to observe significant differences in TAI among tumor bearing and nontumor bearing animals raises doubt in part, of the immunogenicity of the G subline tumor and its appropriateness, at least for subsequent immunological studies. Further factors considered in this regard, are questions of tumor load, including the possible need for the use of adjuvant, and the parameters and sensitivity of immune responsiveness selected for evaluation and immunocompetency. Subsequent evaluation of the effect of TF on other more immunogenic variant sublines of the Dunning R-3327 rat tumor may yet provide further and more useful information.