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At least 73 records · Page 4Linked to original sources
PubMed2002

Melatonin fails to modulate immune parameters influenced by calorie restriction in aging Fischer 344 rats.

The aim of this study was to determine if long-term treatment with melatonin (MEL), a purported anti-aging agent, was as effective as calorie restriction (CR) in modulating immune parameters in aging Fischer 344 male rats. Splenic lymphocytes were isolated from 17-month-old rats that, beginning at 6 weeks of age, were treated with MEL (4 or 16 microg/ml in drinking water) and from 17-month-old rats fed ad libitum (AL) or rats fed a CR diet (55% of AL intake). The number of splenic T cell populations and T cell subsets was measured by flow cytometry, the proliferative response of splenocytes to Concanavalin A (Con A) and lipopolysaccharide (LPS) was measured by [(3)H]thymidine incorporation, and the induction of cytokine production (IL-2 and IFN-gamma) was measured by ELISA assay. In addition, the level of the natural killer (NK) cell activity was assessed by fluorimetric assay. CR rats had a higher number of lymphocytes expressing the naïve T cell marker (CD3 OX22) than AL rats (P < 0.05). CR rats also showed greater induction of proliferative response, IL-2 and IFN-gamma levels following Con A simulation, and NK cell activity than AL rats (P < 0.05). MEL-treated rats did not differ from AL rats in any of these parameters or in any other measurement. These results indicate that MEL treatment is unable to modulate immune function in a manner comparable with that of CR.

Adjuvants, Immunologic↗
PubMed2006

Mycoplasma fermentans and TNF-beta interact to amplify immune-modulating cytokines in human lung fibroblasts.

Mycoplasma can establish latent infections and are associated with arthritis, leukemia, and chronic lung disease. We developed an experimental model in which lung cells are deliberately infected with Mycoplasma fermentans. Human lung fibroblasts (HLF) were exposed to live M. fermentans and immune-modulating cytokine release was assessed with and without known inducers of cytokine production. M. fermentans increased IL-6, IL-8/CXCL8, MCP-1/CCL2, and Gro-alpha/CXCL1 production. M. fermentans interacted with TNF-beta to release more IL-6, CXCL8, and CXCL1 than predicted by the responses to either stimulus alone. The effects of live infection were recapitulated by exposure to M. fermentans-derived macrophage-activating lipopeptide-2 (MALP-2), a Toll-like receptor-2- and receptor-6-specific ligand. The synergistic effect of combined stimuli was more pronounced with prolonged incubations. Preexposure to TNF-beta sensitized the cells to subsequent MALP-2 challenge, but preexposure to MALP-2 did not alter the IL-6 response to TNF-beta. Exposure to M. fermentans or MALP-2 did not enhance nuclear localization, DNA binding, or transcriptional activity of NF-kappaB and did not modulate early NF-kappaB activation in response to TNF-beta. Application of specific inhibitors of various MAPKs suggested that p38 and JNK/stress-activated protein kinase were involved in early IL-6 release after exposure to TNF-beta and M. fermentans, respectively. The combined response to M. fermentans and TNF-beta, however, was uniquely sensitive to delayed application of SP-600125, suggesting that JNK/stress-activated protein kinase contributes to the amplification of IL-6 release. Thus M. fermentans interacts with stimuli such as TNF-beta to amplify lung cell production of immune-modulating cytokines. The mechanisms accounting for this interaction can now be dissected with the use of this in vitro model.

Cells, Cultured↗
PubMed2006

Tumour-induced immune modulation of sentinel lymph nodes.

Sentinel lymph nodes (SLNs), being the first nodes to receive lymph from a primary tumour and the preferential site of initial tumour metastases, are intensively exposed to the bioactive products of tumour cells and other associated cells. This makes them ideal for studies of the factors that determine selective tissue susceptibility to metastases. We postulate that tumour-induced immune modulation of SLNs facilitates lymph-node metastases by inhibiting the generation of tumour-specific cytotoxic T cells that are active against tumour cells of primary and metastatic melanomas. Immune modulation of the lymph nodes can be reversed by granulocyte/macrophage colony-stimulating factor (GM-CSF), a finding that has implications for the future therapy of lymph-node metastases.

Animals↗
PubMed2000

Use of altered peptide ligands to modulate immune responses as a possible immunotherapy for allergies.

Allergies are dramatically increasing in prevalence, and the management of these diseases is a heavy burden on the health-care systems of developed countries. In recent years, many efforts have been made to improve the therapy of allergies and to develop new approaches for immunotherapy. Here we briefly review the use of peptides to modulate T-cell responses to allergens. We focus mainly on the possibility of using altered peptide ligands (APLs), i.e., peptides tailored on immunodominant T epitopes and bearing a single amino-acid substitution, as a tool to modulate immune responses to allergens. These peptides may be recognized by the specific T cells triggered by the agonist peptides, but they are unable to elicit T-cell responses; thus, they could be ideal candidates to modulate immune responses to allergens. The availability of these peptides could allow new approaches for immunotherapies.

Animals↗
PubMed1999

Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole.

OBJECTIVE: To investigate the effects of the immune modulators levamisole and loxoribine in a rat model of endometriosis. DESIGN: Prospective, placebo-controlled study. SETTING: Hospital-based research facility. ANIMAL(S): Nineteen rats with experimentally induced endometriosis. INTERVENTION(S): Rats were treated with three weekly intraperitoneal injections of levamisole (2 mg per rat; n = 6), loxoribine (1 mg per rat; n = 6), or saline (control; n = 7) and killed 8 weeks after treatment. MAIN OUTCOME MEASURE(S): Histologic and immunohistochemical analysis of endometriotic explants. RESULT(S): The loxoribine-treated group showed marked regression of both epithelial and stromal components. Epithelial regression was noted in the control group, but the epithelium was strikingly preserved in the levamisole group. There were significantly greater numbers of dendritic cells in the explants of animals treated with loxoribine and levamisole. The number of natural killer cells was significantly reduced in loxoribine-treated explants. CONCLUSION(S): Loxoribine, a potent immunomodulatory drug, appeared to cause regression in both stromal and epithelium components in a rat model of endometriosis. Further, specific cell-mediated immune responses in this model of endometriosis were elucidated.

Adjuvants, Immunologic↗
PubMed2004

The fibroblast: sentinel cell and local immune modulator in tumor tissue.

Development and progression of epithelial malignancies are frequently accompanied by complex phenotypic alterations of resident tissue fibroblasts. Some of these changes, such as myofibroblastic differentiation and an oncofetal extracellular matrix (ECM) expression profile, are also implicated in inflammation and tissue repair. Studies over the past decade revealed the relevance of reciprocal interactions between tumor cells and tumor-associated host fibroblasts (TAF) in the malignant process. In many tumors, a considerable fraction of the inflammatory infiltrate is located within the fibroblast- and ECM-rich stromal compartment. However, while fibroblasts are known as "sentinel cells" in various nonneoplastic diseases, where they often regulate the composition and function of recruited leucocytes, they are hardly considered active participants in the inflammatory host response in tumors. This article focuses on the functional impact of TAF on immune cells. The complex network of immune-modulating effects transduced by TAF and TAF-derived factors is highlighted, and recent reports that support the hypothesis that TAF are involved in the inflammatory response and immune suppression in tumors are reviewed. The role of TAF-dependent ECM remodeling and TAF-derived peptide growth factors, cytokines, and chemokines in the immune modulation is stressed and the idea of TAF as an important therapeutic target is emphasized.

Animals↗
PubMed2005

Suppression of hepatocellular carcinoma by transplantation of ex-vivo immune-modulated NKT lymphocytes.

NKT cells are a regulatory subset of T lymphocytes with immune modulatory effects and an important role in anti-tumor immunity. The feasibility of "ex-vivo education" of NKT cells has recently been demonstrated. To evaluate the anti-tumor effect of ex-vivo immune-modulated NKT lymphocytes in a murine model of hepatocellular carcinoma. Athymic Balb/C mice were sublethally irradiated and transplanted with human Hep3B HCC. NKT cells prepared from immunocompetent Balb/C mice were pulsed ex vivo with HCC-derived antigens (Group A), Hep3B cells (group B) or BSA (group C), and adoptively transferred into HCC harboring mice (1 x 0(6) NKT cells per mouse). Group D mice did not undergo NKT cell transplantation. Group E mice were transplanted with 1 x 10(6) NKT cells from HBV-immunized donors. Mice were followed for tumor size and weight. To determine the mechanism of the anti-tumor effect, intrasplenic lymphocyte populations were analyzed by FACS for NKT, CD4+ and CD8+ lymphocyte subpopulations; STAT 1, 4 and 6 expression in splenocytes was assessed by Western blot, and serum cytokine levels were measured by ELISA. Adoptive transfer of NKT cells pulsed with HCC-derived antigens (group A) and NKT cells from immunized donors (group E) resulted in complete disappearance of tumors within 4 weeks and attenuated weight loss (6.5% and 7% in groups A and E, respectively). In contrast, mice in groups B, C, and D developed large, necrotic tumors and severe weight loss (21%, 17% and 23% weight loss in groups B, C, and D, respectively). NKT/CD4 and CD8/CD4 ratios were significantly increased in groups A and E (12.3 and 17.6 in groups A and D, respectively, compared to 6.4, 4.8 and 5.6 in groups B, C and D, respectively, for the NKT/CD4 ratio; 41 and 19.8 in groups A and E, respectively, compared to 6.5, 11.8 and 3.2 in groups B, C, and D, respectively, for the CD8/CD4 ratio). Expression of the transcription factor STAT4 was evident in group A, but not in groups B-D. Serum IFNgamma, IL12 and IL4 levels were increased in groups A and E. Adoptive transfer of NKT lymphocytes exposed ex vivo by HCC-derived antigens loaded on dendritic cells and NKT cells from immunized donors led to suppression of HCC in mice. NKT-mediated anti-tumor activity was associated increased NKT and CD8+ T lymphocyte numbers, increased expression of STAT4, a marker for IL-12 activity and elevated serum levels of the proinflammatory cytokines IFNgamma and IL12, and of IL4. Ex-vivo modulation of NKT lymphocytes holds promise as a novel mode of immune therapy for HCC.

Adoptive Transfer↗
PubMed2003

Supplementation of a low-carotenoid diet with tomato or carrot juice modulates immune functions in healthy men.

BACKGROUND: Beta-carotene has been shown to enhance immune functions in humans. Whether vegetables rich in carotenoids, such as beta-carotene or lycopene, modulate immune functions in healthy humans is presently not known. The objective of this study was to investigate the effects of a low-carotenoid diet supplemented with either tomato (providing high amounts of lycopene) or carrot juice (providing high amounts of alpha- and beta-carotene) on immune functions in healthy men. METHOD: In a blinded, randomized, cross-over study, male subjects on a low-carotenoid diet consumed 330 ml/day of either tomato juice (37.0 mg/day lycopene) or carrot juice (27.1 mg/day beta-carotene and 13.1 mg/day alpha-carotene) for 2 weeks with a 2-week depletion period after juice intervention. Immune status was assessed by measuring lytic activity of natural killer (NK) cells, secretion of cytokines (IL-2, IL-4, TNFalpha), and proliferation by activated peripheral blood mononuclear cells. RESULTS: Juice consumption resulted in relatively fast responses in plasma carotenoid concentrations (p < 0.0002) which were not accompanied by concomitant changes in immune functions. For IL-2, NK cell cytotoxicity, and lymphocyte proliferation, maximum responses were observed during depletion periods. The highest production rate was measured only for TNFalpha at the end of the first intervention period. Juice intervention did not modulate the secretion of IL-4. CONCLUSIONS: Increased plasma carotenoid concentrations after vegetable juice consumption are accompanied by a time-delayed modulation of immune functions in healthy men consuming a low-carotenoid diet.

Adult↗
PubMed1992

Psychoneuroimmunology: can psychological interventions modulate immunity?

There is ample evidence from human and animal studies demonstrating the downward modulation of immune function concomitant with a variety of stressors. As a consequence, the possible enhancement of immune function by behavioral strategies has generated considerable interest. Researchers have used a number of diverse strategies to modulate immune function, including relaxation, hypnosis, exercise, classical conditioning, self-disclosure, exposure to a phobic stressor to enhance perceived coping self-efficacy, and cognitive-behavioral interventions, and these interventions have generally produced positive changes. Although it is not yet clear to what extent these positive immunological changes translate into any concrete improvements in relevant aspects of health, that is, alterations in the incidence, severity, or duration of infectious or malignant disease, the preliminary evidence is promising.

Arousal↗
PubMed2006

Immune modulation using mistletoe (Viscum album L.) extracts Iscador.

One repeatedly finds that mistletoe (Viscum album L.) extracts show immune-modulating effects. This is also true in many cases in the experimental setting. Many of the experimental trials cannot, however, be transferred to the clinical situation - or only in a limited way. The aim of this work was to pursue the question of the extent to which the function of immune-competent cells can be influenced by mistletoe extracts. To do this, 3 clinical studies were carried out. Results from the first two studies will be presented here. In a prospective observational study with defined inclusion and exclusion criteria, the impact of two different doses of Iscador M (Malus) or Iscador Qu (Quercus) on the function and number of T-lymphocytes from tumor patients was studied. The immunological tests took place monthly during the first six months. Thirty-one patients were included in the slow dose group and 36 patients in the group with swift dose escalation. It was postulated that too swift increase in dosage would lead to stronger local reactions and impairment of the stimulation capacity of T-cells taken ex vivo and incubated for 72 h. The evaluation showed that patients with stronger local reactions at the injection site have an impairment of mitogen-induced stimulation capacity of T-cells. However, patients with stronger local reaction showed a significant decrease of HLA-DR+ T cells as compared to patients In a GCP-conform, controlled bicentric phase II study the aim was to investigate the efficacy of a perioperative intravenous mistletoe extract application on the modulation of operation-induced immune suppression. For this purpose 105 patients with breast cancer were recruited. At the treatment centre the patients received an infusion of 1 mg Iscador M Spezial prior to the start of an operation, in addition to normal medication, while this was not practised at the control centre. The primary trial objective was the oxidative burst in granulocytes taken from patients ex vivo prior to surgery, and 1 and 3 days after. In order to take account of possible differences in the two groups, propensity scores were used as the basis for a matched pair analysis. It became clear that inhibition of the granulocyte function in the treatment group was significantly less marked (p < 0.001; Wilcoxon). Mistletoe extract-related adverse reactions were not observed. Thus this special form of application could minimise the immune suppression triggered by anaesthesia and operation stress.

Animals↗
PubMed1997

Melatonin, immune modulation and aging.

Melatonin is a hormone secreted by the pineal gland in response to photoperiods and influences many important biological processes. For one, Melatonin has been shown to produce resistance to cancer and infectious diseases in aged animals. Studies in animals have demonstrated melatonin-related mechanisms of action on immunoregulation. Additionally, melatonin has been successfully used in humans, along with interleukin-2, as a treatment of solid tumors. In vivo and in vitro studies show melatonin enhances both natural and acquired immunity in animals. Despite all of this intriguing evidence, melatonin's mechanism of action on the immune system is only partially defined. It does, however, appear to act through lymphocyte receptors, and perhaps, receptors on other immune tissues, to modulate immune cells. In order to understand immunomodulation and anti-cancer effects, information on melatonin and it's interactions with other endocrine hormones are summarized.

Aging↗
PubMed2005

Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2) receptor gene polymorphism: possible risk for autoimmune disorders.

Immune system responsiveness results from numerous factors, including endogenous cannabinoid signaling in immunocytes termed the "immunocannabinoid" system. This system can be an important signaling pathway for immune modulation. To assess the immunomodulating role of the cannabinoid 2 (CB2) receptor, we sought polymorphisms in the human gene, identified a common dinucleotide polymorphism, and investigated its effect on endocannabinoid-induced inhibition of T lymphocyte proliferation. The CB2 cDNA 188-189 GG/GG polymorphism predicts the substitution of glutamine at amino acid position 63 by arginine. T lymphocytes from CB2 188-189 GG/GG homozygotes had approximately twofold reduction of endocannabinoid-induced inhibition of proliferation compared with cells from CB2 188-189 AA/AA homozygotes. In GG/GG subjects, the reduced endocannabinoid inhibitory response was highly significant for N-arachidonylglycine and nearly significant for 2-arachidonylglycerol, and a specific CB2 receptor antagonist partially blocked these effects. Also, patients with autoimmune diseases had an increased prevalence of the homozygous GG/GG genotype. Collectively, these results demonstrate reduced endogenous fatty acid amide immunomodulatory responses in individuals with the CB2 188-189 GG/GG genotype and suggest that this CB2 gene variation may be a risk factor for autoimmunity. The results also support the proposition that the CB2 receptor may represent a novel pharmacological target for selective agonists designed to suppress autoreactive immune responses while avoiding CB1 receptor-mediated cannabinoid adverse effects.

Amino Acid Substitution↗
PubMed2006

Targeting the CB2 receptor for immune modulation.

Early work on the biology of the components of Cannabis sativa showed evidence for a potential influence on immune regulation. With the discovery of a peripheral cannabinoid receptor associated with immune cells, many laboratories have sought to link the immunoregulatory activities of cannabinoid compounds with this receptor, hoping that such compounds would lack the psychoactive effects of marijuana and other nonspecific cannabinoid agonists. In this report, the authors investigate the role of the cannabinoid CB2 receptor in immune regulation, with particular emphasis on compounds shown to regulate immune cell recruitment. The authors conclude by using the immune cell recruitment model to rationalise cannabinoid CB2 receptor-specific effects in modulating immune disease, particularly the increasing evidence for its role in experimental autoimmune encephalomyelitis and in influencing bone density.

Animals↗
PubMed2002

Immune modulation: the genetic approach.

As part of a comprehensive strategy to combat diseases, improving genetically resistance to diseases and therefore immune capacities of animals is more and more desirable. However, research is still needed to develop genetic tools that may be used. In this search, lines selected for various immune responses are used to study relevant immune markers. Chickens have been selected for six generations for three different in vivo immune responses: high antibody response, high cell-mediated immune response and high phagocytic activity. Each line, selected for one trait, showed significant increase in immune capacity for this trait. In addition, results showed clearly independence between the three immune responses analyzed, meaning that a global approach is needed to improve immune capacity. Selected lines allow to follow genetic markers linked to immune response genes. In the different lines, different patterns in MHC gene frequency were observed and MHC alleles differed in their effects according to the immune trait. Some correlations were found between immune responses and production traits. The selected lines will be used to find other "known" immune response genes or "anonymous" genetic markers, which may become the future tools to modulate immune responsiveness of animals.

Animals↗
PubMedDate not supplied

Randomized, double-blind, placebo-controlled trial of the immune modulator WF10 in patients with advanced AIDS.

A randomized, double-blind trial compared treatment with the immune modulator WF10 (ten patients) and placebo (nine patients) administered in cycles over 3 months among individuals with advanced AIDS. There were no notable clinical adverse events; changes in hematologic and chemistry values were comparable in the two groups. In both groups, median HIV-RNA PCR values remained stable. Immunologic variables showed a consistent tendency to increase in the WF10 group and to decrease in the control group, with significant differences between groups for median WBC, lymphocyte, CD19, and CD35 values. Ten infections occurred in the control group, four of which were Pneumocystis carinii pneumonia (PCP), and three in the WF10 group none of which was PCP. Five patients in the control group were hospitalized during the trial for a total of 53 days; no patients in the WF10 group were hospitalized. Over a subsequent 9-months follow-up, six patients from the control group and one from the WF10 group died. These results indicate that WF10 administration appears safe, may enhance immunologic function, and unlike other macrophage-activating cytokines does not increase HIV expression in this patient population. Further studies of WF10 in larger patient populations are warranted.

Adjuvants, Immunologic↗
PubMed1993

Immune modulation of biologic systems in renal somatic cells.

The various theories discussed here suggest that somatic renal cells are susceptible to biologic modulation by the immune system independent of an inflammatory effect. (1) The mode of repression of type IV collagen synthesis by novel, soluble antigen-binding proteins, the down-regulation of class II MHC expression with interruption of antigen presentation to epithelia after selective gene regulation by antibody, and the diverse interactions of antibody with renal glomerular cells producing functional disturbances in endocytosis and permselectivity; (2) modification of surface-antigen composition; (3) alteration of matrix deposition, remodeling and composition; (4) biophysical perturbation of cytoskeletal and cell membrane components; (5) and lastly, alterations in cell adhesion through cell-surface alterations, all lend testimony to the richness of the signal transduction pathways in somatic cells. Although the preceding examples represent only a small fraction of those which may take place within the glomerular and tubular microenvironments, these paradigms may nevertheless serve as new models upon which one can consider the multitude of potential communications between disparate biologic systems that connect in complex organisms.

Animals↗
PubMed2006

Immune modulation and expression of cytokine genes in rainbow trout Oncorhynchus mykiss upon probiotic feeding.

This study elucidates the immune modulation including the expression of cytokine genes following dietary administration of three selected probiotic bacteria--Lactobacillus rhamnosus, Enterococcus faecium and Bacillus subtilis to fish, rainbow trout Oncorhynchus mykiss. They were fed for 45 days on either a basal control diet or one of the three probiotic diets containing the specific bacteria in freeze-dried form at a density of 10(9)CFUgfeed-1. The non-specific immune parameters examined--superoxide anion production by the head kidney leukocytes and the alternate complement activity of serum was improved by probiotic feeding. Besides this, the relative gene expressions of interleukin-1beta1, tumor necrosis factor 1 and 2 and transforming growth factor-beta were up regulated in the spleen and the head kidney. The comparatively better performance of E. faecium could possibly be linked to their suitable ambient temperature conditions. Thus, probiotic bacteria delivered in feed exerts its influence on the immune system of fish, both at cellular and molecular levels.

Animal Feed↗
PubMed2002

NK 1.1+ T cell: a two-faced lymphocyte in immune modulation of the IL-4/IFN-gamma paradigm.

T lymphocytes expressing NK1.1 marker (NK1.1+) have been suggested as being important in peripheral immune modulation. Alteration of the balance between Th1 proinflammatory and Th2 anti-inflammatory cytokine-producing cells can ameliorate immune-mediated disorders. The aim of the study was to determine the role of NK1.1+ lymphocytes in the pathogenesis of tolerance and proinflammatory states and to determine their role in altering the Th1/Th2 balance in experimental colitis. Colitis was induced in C57/B6 mice by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Mice received five oral doses of colonic proteins extracted from TNBS colitis colonic wall. Standard clinical, macroscopic, and microscopic scores were used for colitis assessment. Liver-associated lymphocytes and splenocytes were harvested 14 days following tolerance induction. Depletion of NK 1.1+ lymphocytes was performed 36 hr before lymphocyte harvesting. Lymphocytes were cultured for 12 hr with Con A and colitis extracted proteins. To evaluate the role of NK1.1+ lymphocytes in keeping a balance between immunogenic and tolerogenic subsets of cells, intracellular staining and flow cytometry assays were performed in tolerized and nontolerized mice. IL-4, IL-12, and IFN-gamma levels were measured by ELISA. Administration of mouse-derived colitis-extracted proteins ameliorated experimental colitis. Tolerized mice exhibited significant improvement in all macroscopic and microscopic parameters for colitis. Depletion of NK1.1 following tolerance induction significantly decreased the CD4(+)IL-4(+)/CD4(+)IFN-gamma(+) ratio in tolerized mice. However, depletion of NK1.1 lymphocytes in nontolerized mice increased the CD4(+)IL-4(+)/CD4(+)IFN-gamma(+) ratio, compared with nondepleted nontolerized mice. Induction of tolerance led to an increase in IL4 and a decrease in IFN-gamma levels. In the experimental colitis model NK1.1+ lymphocytes play a dual role: In the presence of peripheral tolerance they may be accountable for keeping the high CD4(+)IL-4(+)/CD4(+)IFN-gamma(+) ratio and disease alleviation. However, in nontolerized conditions they may induce a proinflammatory shift.

Administration, Oral↗