SEARCH · PubMed Health

Results for “immunomodulation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources

PubMed1986

Evaluation of the mechanisms involved in sodium diethyl dithiocarbamate-induced immunomodulation using the hydrophilic analog, sodium N-methyl-D-glucamine dithiocarbamate.

Sodium diethyl dithiocarbamate (DE-DTC) is a lipophilic low molecular weight sulphur compound previously demonstrated to be a potent immunomodulator but cytotoxic in vitro. In this work, we studied the effects on a hydrophilic analog of DE-DTC, sodium N-Methyl-D-glucamine dithiocarbamate (NMG-DTC) on immune responses to a hapten carrier conjugate and on mitogen-induced lymphoproliferation. NMG-DTC, in contrast to DE-DTC, did not modify the responses to a hapten-carrier conjugate. The immunomodulatory activity of DE-DTC appeared to be linked with its lipophilicity. NMG-DTC had a slight inhibitory effect on thymidine incorporation by lymphocytes stimulated by mitogens as compared to that of DE-DTC. DE-DTC was cytotoxic possibly at the cell membrane level; cytotoxicity was not related to the chelating properties of DE-DTC in the culture medium. On the other hand, NMG-DTC appeared to be a less cytotoxic molecule. Therefore it could be useful to study the effects of the dithiocarbamate moiety at the cellular level.

Adjuvants, Immunologic↗

PubMed1987

New immunomodulator lobenzarit disodium (CCA): activation of IgE class-specific suppressor T lymphocytes and regulation of IgE antibody response enhanced by sublethal X-irradiation in SJL/J mice.

The effect of the new immunomodulator lobenzarit disodium (CCA, disodium-2,2'-iminodibenzoate) on IgE antibody response was studied in X-irradiated SJL/J mice. IgE antibody response to dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH) was enhanced by sublethal X-irradiation (400 R), and this enhanced IgE production was suppressed by unprimed normal spleen cell transfer. Oral administration of CCA, every day from 1 day after immunization with DNP-KLH to 1 day before bleeding out, reduced IgE antibody response in sublethally X-irradiated SJL/J mice. The suppressive effect of CCA in the mice was exerted at an early stage of the IgE antibody response. Moreover, CCA showed IgE class-specific suppression and did not suppress IgG class antibody production. CCA-induced reduction of IgE antibody response in SJL/J mice seems to be mediated by suppressor T cells, since depletion of T cells by treatment with antithymocyte serum and complement abolished the CCA-induced reduction and splenic T cells from CCA-treated mice were able to transfer the suppressive effect.

Animals↗

PubMed2004

Therapy of ischemic cardiomyopathy with the immunomodulating agent pentoxifylline: results of a randomized study.

BACKGROUND: Inflammatory immune activation commonly occurs in heart failure and may perpetuate this syndrome. We sought to determine whether the immunomodulating agent pentoxifylline enhances left ventricular function in patients with ischemic cardiomyopathy. We also investigated the effect of therapy on levels of brain natriuretic peptide (NT-pro BNP), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and the marker of apoptosis, Fas/Apo-1. METHODS AND RESULTS: In a single-center, prospective, randomized, double-blind, placebo-controlled study, 38 patients with ischemic cardiomyopathy received pentoxifylline 400 mg TID or placebo in addition to standard therapy. Clinical assessment, radionuclide ventriculography, echocardiography, and blood analyses were performed at baseline and after 6 months. There were no differences in baseline characteristics between the groups. Five patients died (4 in the placebo group). Pentoxifylline treatment resulted in an improvement in functional class (P<0.005) and an increase in systolic blood pressure (P<0.05) and left ventricular radionuclide ejection fraction (P<0.05) compared with the placebo-treated group. There were reductions in plasma concentrations of CRP, NT-pro BNP, TNF-alpha, and Fas/Apo-1 in the pentoxifylline compared with the placebo-treated group. CONCLUSIONS: In patients with heart failure due to ischemic left ventricular dysfunction, the addition of pentoxifylline to standard therapy results in improvements in clinical status and radionuclide ejection fraction, which are accompanied by reductions in plasma markers of inflammation, prognosis, and apoptosis.

Adjuvants, Immunologic↗

PubMed2001

Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure.

BACKGROUND: Congestive heart failure (CHF) is characterized by enhanced immune activation, and immune-mediated mechanisms may play a pathogenic role in this disorder. Based on the immunomodulatory effects of intravenous immunoglobulin (IVIG), we hypothesized that IVIG could downregulate inflammatory responses in CHF patients and have potential beneficial effects on the left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Forty patients with chronic symptomatic CHF and LVEF of <40%, stratified according to cause (ie, ischemic and idiopathic dilated cardiomyopathy), were randomized in a double-blind fashion to receive therapy with IVIG or placebo for a total period of 26 weeks. Our main findings were that (1) IVIG, but not placebo, induced a marked rise in plasma levels of the anti-inflammatory mediators interleukin (IL)-10, IL-1 receptor antagonist, and soluble tumor necrosis factor receptors; (2) significantly correlated with these anti-inflammatory effects, IVIG, but not placebo, induced a significant increase in LVEF from 26+/-2% to 31+/-3% (P:<0.01), and this was found independent of the cause of heart failure; and (3) N-terminal pro-atrial natriuretic peptide decreased significantly after induction therapy and continued to decrease toward the end of study during IVIG therapy (P:<0.001) but remained unchanged during placebo. CONCLUSIONS: We demonstrated an IVIG-induced change in the balance between inflammatory and anti-inflammatory cytokines that favored an anti-inflammatory net effect in CHF. This effect was significantly correlated with an improvement in LVEF, suggesting a potential for immunomodulating therapy in addition to optimal conventional cardiovascular treatment regimens in CHF patients.

Adjuvants, Immunologic↗

PubMed1985

Cyclosporine immunomodulation in a rabbit model of chronic hypersensitivity pneumonitis.

Rabbit models of chronic experimental hypersensitivity pneumonitis and desensitization were used to evaluate the effects of systemic cyclosporine. When administered 12 to 18 h before each inhalational challenge with aerosolized antigen and the adjuvant muramyl dipeptide, cyclosporine suppressed the development of disease as well as the anamnestic antibody response, particularly in bronchoalveolar lavage fluids. When administered at the time of sensitization only, cyclosporine suppressed the primary antibody response but not the anamnestic antibody response or the disease. Antigen- and mitogen-induced blastogenesis was inhibited by cyclosporine in vitro, but antigen-specific blastogenesis was not abrogated by cyclosporine previously administered in vivo. These results indicate that cyclosporine caused profound immunomodulation in this model, which can be at least partially explained by transient suppressive effects on T cells, particularly the helper/inducer and delayed hypersensitivity subset(s).

Alveolitis, Extrinsic Allergic↗

PubMed1994

Treatment of virus-induced myocardial injury with a novel immunomodulating agent, vesnarinone. Suppression of natural killer cell activity and tumor necrosis factor-alpha production.

Controversy still exists concerning the therapy for viral myocarditis which manifests a wide variety of clinical symptoms. Vesnarinone, a quinolinone derivative that was developed as a positive inotropic agent with complex actions, including phosphodiesterase inhibition and cation channel modification, has recently been confirmed to improve the prognosis of patients with chronic heart failure. However, the precise mechanism of this beneficial effect is not yet clearly understood. In this study, using a murine model of acute viral myocarditis resulting from encephalomyocarditis virus infection, survival and myocardial damage were markedly improved by treatment with vesnarinone. In contrast, survival was not improved by treatment with amrinone, a phosphodiesterase inhibitor. Although vesnarinone did not inhibit viral replication or protect myocytes from viral direct cell injury, it did inhibit the increase in natural killer cell activity after viral infection. On the other hand, amrinone failed to inhibit natural killer cell activity. Both vesnarinone and amrinone suppressed the production of tumor necrosis factor-alpha. Therefore, we postulate that vesnarinone exerted its beneficial effects through an inhibition of natural killer cell activity, and that it serves as an immunomodulator providing new therapeutic possibilities for the treatment of viral myocarditis and/or immunological disorders.

Amrinone↗

PubMed2005

FTY720, a novel immunomodulator in de novo kidney transplant patients: pharmacokinetics and exposure-response relationship.

The pharmacokinetics, safety, and preliminary efficacy of FTY720, a novel immunomodulator, were examined in de novo renal transplant patients. Both noncompartmental and population methods were used to estimate pharmacokinetic estimates in the patients. The steady-state plasma concentrations of FTY720 increased in accordance with maintenance dose level, indicating linearity in clearance and volume of distribution over the 0.25- to 2.5-mg dose range. The pharmacokinetics of FTY720 in de novo renal transplant patients were characterized by the long terminal phase half-life of approximately 200 hours across doses, high volume of distribution (>3000 L), and low clearance (10.8 L/h). The intersubject variation of clearance was 55%, and the intrasubject variation of FTY720 concentrations was 28%. The population analysis revealed significant positive relationships between baseline alkaline phosphatase and clearance, as well as between baseline body weight on apparent volume of distribution. There was no relationship between FTY720 concentrations within a given FTY720 dose cohort and the rate of allograft rejection.

Adult↗

PubMed1995

Immunomodulating effects of synchronised plasmapheresis and intravenous bolus cyclophosphamide in systemic lupus erythematosus.

Recent studies have suggested that synchronised plasmapheresis and intravenous pulse cyclophosphamide therapy reduce disease activity in SLE patients. The aim of the present study was to examine the immunomodulating effects of this therapy and compare it with changes seen with cyclophosphamide alone. Four patients with active SLE were studied. Two were treated with synchronised therapy and two received cyclophosphamide only for up to 26 weeks. Disease activity was measured by the SLE disease activity index (SLEDAI). Immunological studies were performed immediately prior to each treatment. Patients in both treatment groups improved as reflected by a fall in mean SLEDAI scores: synchronised therapy 33.5 to 11; cyclophosphamide only 13.5 to 4.5. Following synchonised therapy only there was a prompt and sustained increase in the mean percentage of CD8+ cells (20.8 to 54.8) which resulted in a fall in the CD4:CD8 ratio (1.95 to 0.62). With both treatment modalities there was a fall in the proportion of CD20+ cells (B lymphocytes) (synchronised therapy 10.5 to 3.2; cyclophosphamide only 5.6 to 2.2). However, only synchronised therapy resulted in a fall in the in vitro production of immunoglobulins which was unchanged or increased following cyclophosphamide alone. These results suggest that although both treatment modalities are efficacious in the treatment of active SLE they produce different immunomodulatory effects. Thus, both therapies reduce the number of circulating B lymphocytes whereas synchronised therapy also modifies cellular immunity by promoting the emergence of a phenotypic suppressor T lymphocyte population.

Adjuvants, Immunologic↗

PubMed1996

Immunomodulation of experimental APS: lessons from murine models.

During the last few years several murine models for APS have been described. These include spontaneous occurring disease, or APS induced by immunization with pathogenic autoantibodies. Employing those models, several treatment modalities, in different stages of the disease, were studied. Treatments which showed promising potential for application in patients with APS include immunomodulation with specific anti-idiotypic or anti-CD4 antibodies, treatment with IL-3, high-dose intravenous immunoglobulins, ciprofloxacin or bromocriptine, as well as antithrombotic and anticoagulant treatments using aspirin and/or low-molecular-weight heparin. Bone-marrow transplantation was also found to improve clinical and serological manifestations of the disease. These studies might promote the handling of controlled clinical trials assessing their efficacy in APS patients.

Animals↗

PubMed1990

Cimetidine: an immunomodulator.

Suppressor T lymphocytes possess histamine2 (H2) receptors and contribute significantly to the function of the immune system. Experimentally, cimetidine, an H2-receptor antagonist, has been shown to enhance a variety of immunologic functions both in vivo and in vitro because of its inhibitory effects on suppressor-cell function. Successful tumor immunotherapy, as well as some protection from infection, has been reported in experimental animals. Patients receiving cimetidine have been shown to exhibit enhanced cell-mediated immunity as evaluated by increased response to skin-test antigens, restoration of sensitivity following development of acquired tolerance, and increased responses of lymphocytes to mitogen stimulation. Preliminary reports also indicate that cimetidine may offer therapeutic benefits for patients with Varicella zoster and Herpes simplex infections, as well as those suffering from mucocutaneous candidiasis and common variable hypogammaglobulinemia. These immunoregulatory effects are dose-related but are not always consistent. Because of its inhibitory effect on suppressor function, cimetidine treatment may be deleterious in patients with organ transplant and autoimmune disorders. Cimetidine should be used as an immunomodulator on an experimental basis only.

Adjuvants, Immunologic↗

PubMedDate not supplied

Allopurinol has immunomodulating activity following topical and systemic application in experimental autoimmune uveitis.

PURPOSE: Allopurinol has beneficial effects in the systemic treatment of lens-induced uveitis and experimental autoimmune uveitis (EAU). This is believed to be due to a reduction of oxidative tissue damage through its dose-dependent free radical scavenging ability, and to an immunomodulating effect. The purpose of this study was to demonstrate the immunological effects on the IgG-antibody repertoire in EAU after topical and systemic allopurinol and steroids. METHODS: We assigned 43 male Lewis rats to 6 different groups: healthy rats (BASE, n=3)

Adjuvants, Immunologic↗

PubMed1995

Transient immunomodulation by intravenous methylprednisolone treatment of multiple sclerosis.

The extent and duration of immunomodulation induced by high-dose corticosteroid treatment of clinical relapse of multiple sclerosis was investigated. Ten patients treated with a 5 day course of intravenous methylprednisolone (IVMP) (500 mg daily) were studied. Circulating lymphocyte subpopulations and mitogen-induced interleukin 2 (IL-2) and gamma-interferon (gamma-IFN) production were determined immediately before initiation of therapy (day 1), during therapy (24 h after first dose, day 2) and at 24 h and 1 week post therapy (days 6 and 12 respectively). T-cell subpopulation (CD3, CD4, CD8, CD4CD45RA, CD4CD45RO) levels fell within 24 h of initiation of therapy, rebounded above pretreatment levels at day 6 and normalised 1 week post therapy. Despite a reduction in total T-cell numbers during treatment, the gamma delta T-cell subpopulation was not significantly altered. HLA-DR expression on B cells and monocytes declined transiently on day 2 to approximately 50% of pretherapy levels. IL-2 and gamma-IFN production were reduced during therapy but returned to baseline levels by 24 h post therapy. The effects of IVMP on lymphocyte distribution and function appear to be short-lived and, therefore, may not be responsible for the rapid improvement associated with this form of treatment.

Adjuvants, Immunologic↗

PubMed1998

Immunomodulating functions of recombinant ovine interferon tau: potential for therapy in multiple sclerosis and autoimmune disorders.

The interferons (IFN) are a family of complex proteins possessing antiviral, antiproliferative, and immunomodulatory activities. Two type I recombinant human IFN have been recently approved for the treatment of multiple sclerosis (MS). However, use of high dose type I IFN treatment in MS patients has been limited by dose-related toxicity. Ovine IFN tau is a unique type I interferon discovered for its role in the animal reproductive cycle. It differs from other type I IFNs in that it is remarkably less toxic even at high concentrations, is able to cross species barriers, and is not inducible by viral infection. Ovine IFN tau has been shown to be very effective in the treatment of animal models of MS. In this study, we examined the toxicity of OvIFN tau on human T-cells at high doses and its immunregulatory properties at equivalent doses. Our experiments confirmed the remarkably non-toxic nature of OvIFN tau on human cells at high concentrations as well as immunomodulating properties consistent with other type I IFNs including an antilymphoproliferative effect and inhibition of IFN gamma-induced HLA class II expression. These results suggest that OvIFN tau could be developed into a potentially less toxic therapeutic option for immune-mediated disorders including MS.

Antigen Presentation↗

PubMed2005

Significant reduction of laparotomy-associated lung metastases and subcutaneous tumors after perioperative immunomodulation with flt3 ligand in mice.

Laparotomy has been associated with increased rates of tumor establishment and metastasis formation postoperatively in animal models. The purpose of this study was to determine the impact on postoperative tumor growth of perioperative upregulation of immune function via fetal liver tyrosine kinase 3 (Flt3 ligand). Two murine studies were carried out: the first utilized a lung metastases model, and the second involved a subcutaneous tumor model. Each study included four groups: anesthesia control (AC), AC plus Flt3 ligand (ACFlt3), sham laparotomy (OP), and OP plus Flt3 ligand (OPFlt3). Flt3 ligand was administered by daily intraperitoneal injection (10 mug/dose) beginning 5 days preoperatively and continuing for 1 week postoperatively. In study 1, A/J mice were given tail vein injections of 1.5 x 10(5) TA3Ha cancer cells on the day of surgery. The mice were sacrificed 14 days after surgery, the lungs processed, and the surface metastases counted by a blinded observer. In study 2 C3H/He mice were given a dorsal subcutaneous injection of 10(4) MC-2 cancer cells on the day of surgery. The mice were sacrificed 31 days after surgery, and the injection sites were evaluated for subcutaneous tumors grossly and histologically. In study 1, the median number of surface lung metastases per mouse was 166 in the OP group and 38 in the OPFlt3 (P = .021). Mice in the AC group developed a median 50 lung metastases per animal compared with mice in the ACFlt3 group who had a median of 10 metastases per mouse (P = .001). The OP group had significantly more metastases than the AC group (P = .048). In study 2, the percentage of animals that developed tumors in the AC, OP, ACFlt3, and OPFlt3 groups was 43, 80, 0, and 20, respectively. The incidence of tumors in the OPFLt3 group and the ACFlt3 group was significantly less than their respective control groups (P < .01). The difference between the OP and AC groups was not significant (P > .05). Perioperatively administered Flt3 ligand was associated with significantly fewer lung metastases and a lower incidence of subcutaneous tumor formation after laparotomy and anesthesia alone. Perioperative immunomodulation may limit untoward surgery-related oncologic effects.

Adenocarcinoma↗

PubMed1999

Prophylaxis with the novel immunomodulator pidotimod reduces the frequency and severity of upper respiratory tract infections in children with Down's syndrome.

Down's syndrome (DS) is associated with several defects of both specific and non-specific immunity which may explain the enhanced susceptibility of DS subjects to viral and bacterial infections. In this study we have evaluated the effects of the new synthetic immunomodulator pidotimod in recurrent infections of the upper respiratory tract in a group of children with DS. It was an open trial vs untreated control, the pidotimod-treated group consisted of 14 subjects and the control group of 12. Pidotimod was administered at the dose of one 400 mg oral bottle/day for 90 days. There was a significant reduction in the frequency, severity and duration of infectious episodes in the pidotimod-treated group vs the untreated control group. The beneficial effects of pidotimod were also confirmed by a series of recordings made over the 90-day treatment period which showed a significant reduction in the number of days of fever, severity of the signs and symptoms of the acute episodes and use of antibiotics and antipyretic drugs. Pidotimod was well tolerated and no clinical, hematological or biochemical side-effects were noted.

Adolescent↗

PubMed2001

Antifungal and immunomodulating activities of 1,4-benzothiazine azole derivatives: review.

We reviewed the studies on the in vitro and in vivo antifungal activity of 1,4-benzothiazine azole derivatives (1,4-BT). A number of different 1,4-BT have been tested for anti-Candida activity, investigating their N-4 substitution, sulfur oxidation state, presence of the carbonyl group in C-3, insertion of the side chain on C-6, C-7 or C-8 of benzothiazine nucleus, the nature of azolic substituent (triazole or imidazole), which tend to differ. Moreover, benzoxazine analogues have been tested to evaluate the effect of sulfur bioisosteric substitution on their activity. We found that their antifungal activity correlates with well-defined chemical characteristics including the presence of ether substitution at the side chain. In fact, ether derivatives are the most active compounds in vivo, although they have little anti-Candida effect in vitro. This discrepancy could be attributed to the fact that 1,4-BT are metabolized to active antifungal compounds and may have in vivo activity through improvement of protective immune response and direct antifungal effects. In fact, 1,4-BT also show immunomodulating activity so that the direct antifungal activity, in combination with the capability to stimulate the immune response, could result in a significant increase in in vivo efficacy.

Animals↗

PubMed2001

Desirable and undesirable immunotropic effects of antibiotics: immunomodulating properties of cefaclor.

The effect exerted on complex immunoregulatory functions of the immune system is an important criterion when selecting an antibiotic. When assessing the effect of an antibiotic on the immune system, one should also take into consideration the existence of functional relationships between the immune system and the nervous and hormonal systems. Among these three systems, there are common factors that modify biological processes. This makes it possible for the antibiotic not only to interact directly with the elements of the immune system, but also to exert indirect influences on potential neurotropic and endocrinotropic effects of the drug. Besides highly effective bactericidal activity, cefaclor demonstrates the ability to exert a favorable effect on some of the specific and non-specific immune responses and immunoregulation mechanisms, which may be important from a clinical point of view. Cefaclor enhances phagocytosis and bactericidal activity of granulocytes and macrophages, and favorably modifies the cooperation of monocytes and T lymphocytes. In this way, it corrects, both in vivo and in vitro, the immunoregulatory disturbances induced and aggravated by an infection. This effect is reflected by an improvement in the impaired immunoregulating activity of T lymphocytes, and is manifest both as an increase in suppressive activity and a correction of the monokine level ratio in relation to the decrease of proinflammatory monokine IL-1 and a relative increase of antiinflammatory IL-1ra. By normalizing the disturbed immunoregulation mechanism, cefaclor enhances the protective potential of the immune reaction while it also reduces the risk of immunogenic clinical complications such as persistent inflammatory conditions and allergic and/or autoaggressive responses. Such immunomodulating properties of cefaclor may be useful in the clinical treatment of patients with immune disorders leading to chronic inflammation and secondary allergic or autoaggressive reactions.

Adjuvants, Immunologic↗

PubMed2005

ProtEx: a novel technology to display exogenous proteins on the cell surface for immunomodulation.

Gene therapy as an immunomodulatory approach has the potential to treat various inherited and acquired immune-based human diseases. However, its clinical application has several challenges, varying from the efficiency of gene transfer, control of gene expression, cell and tissue targeting, and safety concerns associated with the introduction of exogenous DNA into cells/tissues. Gene therapy is also a time- and labor-intensive procedure. As an alternative, we recently developed a novel technology, ProtEx, that allows for rapid, efficient, and durable display of exogenous proteins on the surface of cells, tissues, and organs without detectable toxicity. This technology exploits the strong binding affinity (Kd = 10(-15) M) of streptavidin with biotin and involves generation of chimeric molecules composed of the extracellular portions of immunological proteins of interest and a modified form of streptavidin, biotinylation of biological surfaces, and decoration of the modified surface with chimeric proteins. Biotin persists on the cell surface for weeks both in vitro and in vivo, thereby providing a platform to display exogenous proteins with extended cell surface kinetics. Two chimeric proteins, rat FasL (SA-FasL) and human CD80 (CD80-SA), were generated and tested for cell surface display and immunomodulatory functions. SA-FasL and CD80-SA molecules persisted on the surface of various cell types for extended periods, varying from days to weeks in vitro and in vivo. The cell surface kinetics, however, were protein and cell type dependent. SA-FasL showed potent apoptotic activity against Fas+ cells as a soluble protein or displayed on the cell surface and effectively blocked alloreactive responses. The display of CD80-SA on the surface of tumor cells, however, converted them into antigen-presenting cells for effective stimulation of autologous and allogeneic T-cell responses. ProtEx technology, therefore, represents a practical and effective alternative to DNA-based gene therapy for immunomodulation.

Animals↗