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Results for “immunomodulation”

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PubMed2004

The influence of immunomodulation on psycho-neuroimmunological functions in benign multiple sclerosis.

OBJECTIVES: In multiple sclerosis (MS), several neuroimmunomodulatory effectors are known, including melatonin. They are able to influence disease-related neurophysiogical changes (disability or impaired vision) as well as neuropsychological performance (e.g. cognition and depression). In this study we assessed the relationship between immunomodulation on psycho-neuroimmunological functions in benign multiple sclerosis. METHODS: We evaluated 26 young female patients with benign MS treated with/without immunomodulating therapies with regard to their physical disabilities (Expanded Disability Status Scale, EDSS), their visually evoked potentials (VEP), their plasma melatonin concentrations as well as their performance regarding emotional and cognitive tests and compared them with healthy matched controls. RESULTS: Patients with MS showed deficits in cognitive and emotional functions compared to healthy controls, which were in accordance with their increase in EDSS over time. However, in contrast to untreated patients, patients receiving immunotherapy showed significantly increased dysfunction with respect to actual mood (p = 0.02) and a tendency to increased depression scores (p = 0.072). However, neither treatment subgroup had cognitive deficits. In untreated patients, melatonin levels correlated with reduced scores in the cognitive tests (p = 0.045) but not with depression or VEP latencies. Patients with long-standing MS (>10 years) showed a significant correlation (p = 0.01) to their increased depression scores and their melatonin levels, but no correlation with VEP or cognitive dysfunction, compared to patients with shorter disease duration (< or =10 years). CONCLUSION: These results indicate that in MS all aspects of the psycho-neuroimmunological network can be affected. Despite the potential influence of immunomodulation on depression, no connection with melatonin representing the retinohypothalamic tract/pineal gland circuits could be detected. However, visual perception as well as visuoconstructive abilities were affected in MS patients. Neuropsychological tests in MS should concentrate on cognitive variables, which reflect the clinical status more accurately and may be used to monitor disease-modifying therapies.

Adult↗

PubMed2006

Novel therapies for Crohn's disease: focus on immunomodulators and antibiotics.

OBJECTIVE: To review the literature on novel immunomodulators such as tumor necrosis factor alpha (TNF-alpha)- and interleukin (IL)-related agents, 6-thioguanine (6-TG), tacrolimus, and leflunomide, and antibiotics such as ornidazole, rifaximin, and ciprofloxacin for the treatment of Crohn's disease. DATA SOURCES: Literature was accessed through MEDLINE (1966-January 2006) using the terms Crohn's disease, novel therapies, immunomodulators, and antibiotics. Article references were hand-searched for additional relevant articles and abstracts. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated. Studies including greater than 5 patients with primarily adult populations were included in the review. DATA SYNTHESIS: There are a number of new TNF-alpha and IL-related agents that may be useful for management of Crohn's disease. They include CDP 571, CDP 870, etanercept, onercept, thalidomide, IL-10, and IL-11. Several studies have shown that CDP 571 decreases the Crohn's Disease Activity Index score and is promising, especially in patients with refractory disease. 6-TG, tacrolimus, and leflunomide are among other immunomodulators that appear to have a role in refractory/severe disease. Finally, ornidazole, rifaximin, and ciprofloxacin are antimicrobials that may be used in patients who have failed other therapies or as adjunctive therapies. CONCLUSIONS: A number of new treatment modalities are being investigated for Crohn's disease. Many of them are promising, and some of these agents may be considered in treatment-refractory patients in the future. However, some of the agents reviewed here are not available in the US. Future studies need to be double-blinded and placebo- or other treatment-controlled in a more homogeneous patient population.

Animals↗

PubMed2002

Expression of immunomodulating molecules by recombinant viruses: can the immunogenicity of live virus vaccines be improved?

Several obstacles exist for the development and use of live attenuated vaccines, including difficulty in achieving a proper balance between attenuation of viral replication and immunogenicity; inducing a strong T-helper 1 response in early life when the immune system is T helper 2 biased and immunization is sometimes associated with immunopathology and the immunosuppressive effect of maternal antibodies in infants. For some viral infections, the immune response to natural infection does not confer solid protection, complicating the task of vaccine development. The development of methods for generation of recombinant viruses provided new opportunities for improving the immunogenicity of live virus vaccine candidates, including the construction of viruses that express cytokines or other immunomodulating molecules. Depending on the choice of immunomodulating molecule, various stages of the immune response can be affected, such as antigen presentation or T-cell proliferation and differentiation. In addition to using the approach for development of viral live attenuated vaccines, it is currently being explored for the development of antitumor vaccines. For this type of vaccine, expression of tumor antigens and one or more immunomodulating molecules by one or several recombinant viruses has been proposed.

Adjuvants, Immunologic↗

PubMedDate not supplied

Effect of an immunomodulator on the efficacy of an attenuated vaccine against avian pneumovirus in turkeys.

Since 1997, avian pneumovirus (APV) has caused estimated annual losses of $15 million to the Minnesota turkey industry. In order to develop an attenuated live vaccine against APV, we serially passaged a Minnesota isolate of APV (APV/MN/turkey/1-a/97) in vitro in cell cultures for 41 passages. Laboratory experiments with this high-passage virus (P41) indicated that the attenuated virus provided immunogenic protection to turkeys against challenge with virulent APV, although some birds showed mild to moderate dinical signs after inoculation. To reduce the residual pathogenicity of P41, while maintaining its immunogenicity, we decided to vaccinate turkeys with P41 in the presence of an immunomodulator, S-28828 (1-n-butyl-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-4-amine-hydrochloride), which is a potent cytokine inducer. The combined inoculation of S-28828 (5 mg/kg body weight) and P41 resulted in a significant reduction in the incidence of virus-induced clinical signs in comparison with birds that received P41 without immunomodulator (P < 0.05). Only 17% of birds inoculated with S-28828 + APV P41 showed mild respiratory symptoms at 5 days postinoculation as compared with 46% of the vaccinated turkeys that did not receive S-28828. Vaccination with either P41 or with P41 + S-28828 protected turkeys against dinical signs and viral replication after challenge with virulent APV. These results indicate that immunomodulators, such as S-28828, may act as good vaccine adjuvants that can reduce the pathogenicity but maintain the immunogenicity of partially attenuated vaccines.

Adjuvants, Immunologic↗

PubMed2006

Topical macrolide immunomodulators: a role in the treatment of vitiligo?

Recently, topical macrolide immunomodulators have been successfully introduced in the treatment of atopic dermatitis. With the growing interest in this new line of topical immunosuppressants, research into the efficacy of these medicines in other T-cell-mediated skin diseases, such as psoriasis, lichen planus, and even vitiligo, is expanding rapidly. It is generally accepted that autoimmune factors play an important role in vitiligo. In this article, the possible use and mechanism of topical macrolide immunomodulators in the treatment of vitiligo are discussed, together with the current state of clinical studies and case reports. These limited reports indicate that topical macrolide immunomodulators may play a role in the treatment of vitiligo, particularly in areas where use of potent corticosteroids is contraindicated.

Administration, Cutaneous↗

PubMed1988

Immunomodulation: a means of disease prevention in stressed livestock.

The ability to stimulate the immune response of cattle and pigs offers a new means of disease intervention. This review discusses current in vivo experiments that have evaluated immunomodulators in cattle and pigs. Levamisole, thiabendazole, imuthiol, avridine, isoprinosine, bovine recombinant interferon, human recombinant interleukin-2, bovine recombinant interleukin-2 and various supplemental vitamins and minerals have been used as immunomodulators in livestock with various degrees of success. Future research on immunomodulators, specific for domestic farm animals, will provide additional methods of treating immunosuppressed animals.

Animals↗

PubMed1995

Comparison of immunomodulative effects of the histamine-2 receptor antagonists cimetidine, ranitidine, and famotidine on peripheral blood mononuclear cells in gastric cancer patients.

BACKGROUND: Histamine-2 receptor antagonist (H2-RA) have been shown to improve the function of various parts of the immune system. The proposed mechanism of the immunomodulative effects of H2-RA has been considered to be the inhibition of suppressor T-lymphocyte activity, an increase in interleukin-2 production, and an enhancement of natural killer cell activity. Most of these studies were done with cimetidine. Comparative data with other H2-RA are limited and conflict on immunomodulative effects. Comparison of the actions of H2-RA on the immune system is required. METHODS: We compared the immunodulative effect of the H2-RAs cimetidine, ranitidine, and famotidine on peripheral blood mononuclear cells (PBMC) in normal controls and patients with gastric cancer. DNA synthesis, cytotoxicity against K562 cells, and the levels of soluble interleukin-2 receptor (sIL-2R) in supernatant were measured after addition of the various H2-RA to PBMC cultures. RESULTS: Subjects with gastric cancer showed significantly higher levels of suppressor lymphocyte activity than normal controls. These levels were restored to levels of normal controls by the addition of cimetidine. Statistically significant lymphoblastogenesis and cytotoxicity against K562 cells were observed only in cimetidine-treated PBMC (p < 0.05); such effects were not observed in ranitidine- or famotidine-treated PBMC. Significantly increased levels of sIL-2R were found in supernatants obtained from culture flasks treated with cimetidine and phytohemagglutinin or ranitidine and phytohemagglutinin (p < 0.01). CONCLUSIONS: Of the three H2-RAs tested, cimetidine had the strongest and famotidine the weakest immunomodulating effect. Only cimetidine augmented the cytotoxicity and proliferative response of lymphocyte to mitogen; neither ranitidine nor famotidine had such an effect. These results might be due to their structural differences. In addition, the immunologic effects of H2-RA are unlikely to be mediated via specific interaction at the H2 receptor.

Adjuvants, Immunologic↗

PubMed1984

Dissociative effects of a novel immunomodulating agent (CP-20, 961) on host defenses of mice.

The antimicrobial and antitumor effects of CP-20,961, a synthetic lipoid amine with immunomodulating properties, were investigated. Mice given CP-20,961 ip seven or three days before challenge with ip Listeria monocytogenes had a lower mortality than control mice. By contrast, CP-20,961 did not protect against lethal challenges of either Salmonella typhimurium or Toxoplasma gondii. In parallel with the in vivo studies, peritoneal macrophages from CP-20,961-injected mice inhibited multiplication of L. monocytogenes but not T. gondii. Further studies demonstrated that CP-20,961 protected mice against an ip challenge of P815 tumor cells as measured by survival time. This correlated with the ability of stimulated peritoneal macrophages to inhibit (3H-TdR uptake inhibition) and kill (Cr51 release) P815 cells in vitro. These data indicate that CP-20,961 affords protection against an ascitic mastocytoma tumor line and at least one, but not all, intracellular pathogens. The dissociation of the immunomodulating effect, which was reflected in peritoneal macrophage function, may be characteristic of this new class of immunomodulators.

Adjuvants, Immunologic↗

PubMed1999

Immunomodulation in sepsis: the role of hemofiltration.

Inflammation is a normal and biologically important process essential for host defense and repair of tissue injury. However, given the cyto-destructive capacity of inflammation, it is tightly controlled even in severe sepsis. There are both pro- and anti-inflammatory components of the inflammatory response, which are initiated simultaneously and co-exist in a single organism. Significant morbidity and mortality results when the inflammatory response becomes unstable and its components uncoupled. Restoring immune stability likely requires reestablishing a balance between pro- and anti-inflammatory processes as well as restoring the normal feedback mechanisms necessary for systemic control. Selective manipulation of inflammation by augmenting or blocking specific components continues to fail as a therapeutic approach to human sepsis, perhaps because such targeted manipulation of the immune response is unable to restore balance and immune stability. It has been recently shown that continuous veno-venous hemofiltration (CVVH) can nonselectively affect the plasma concentrations of immune mediators in patients with sepsis and multiple organ dysfunction syndrome (MODS). Hemofiltration offers tremendous potential advantages over other forms of immunomodulation because it is both non-specific and self-regulating. CVVH can remove both soluble pro- and anti-inflammatory substances and does so in direct relationship to the circulating mediator concentrations. The ultimate value of this technique will depend on whether immunomodulation is an appropriate goal for patients with sepsis. The avoidance of unintended immunomodulation is also an important issue, and evidence already suggests that this should be a priority.

Adjuvants, Immunologic↗

PubMedDate not supplied

[Principles of classification and the strategy of immunomodulators used in medicine].

The review deals with problems of the subdivision of the presently known immunomodulators in accordance with the mechanisms of their action on individual elements and systems of immunity. The necessity of immunomodulators systematization according to their purpose with a view to the prophylaxis or therapy of definite diseases caused by the pathology of the immune system or accompanied by its disturbances is emphasized. The approximate scheme and principles of the immunomodulators classification are proposed with due regard to the nature, character and mechanisms of action of the preparations.

Adjuvants, Immunologic↗

PubMedDate not supplied

[Combined use of killed vaccines and immunomodulator ridostin for urgent prevention of epidemic stomatitis, Aujeszky disease and carnivore plague in experiment].

Results of experimental studies of mice and pigs infected with foot-and-mouth disease virus, minks infected with Aujeszky's disease virus, and dogs infected with canine distemper virus are described. In animals with foot-and-mouth disease and Aujeszky's disease, combined treatment with killed vaccine and immunomodulator Ridostin by the scheme of urgent prophylaxis (3 days before infection) caused 75% (foot-and-mouth disease) and 100% (Aujeszky's disease) prevention of animal death and development of generalized infection. The use of Ridostin by the scheme of urgent prophylaxis in a canine distemper infection focus arrested clinical symptoms of the disease in 50% of animals received immunomodulator. Clinical symptoms of canine distemper in the other dogs treated with immunomodulator were manifested in a mild form, and their appearance was delayed to 23-25 days after contact with infected animal.

Animals↗

PubMed1998

Analysis of Immunomodulating Properties of Retinoids.

In this work analysis of immunomodulating properties of retinoids and carotinoids, mainly beta-carotene is presented. The main attention is concentrated on the latest investigations of the role of retinoid receptors in realization of retinoid influence on differentiation of hematopoietic elements and the apoptosis induction. The conclusion concerning the principal advantages of beta-carotene as immunomodulator comparing to other existing immunomodulating agents has been made.

Journal Article↗

PubMed2003

Increases in cytokine and antimicrobial peptide gene expression in horses by immunomodulation with Propionibacterium acnes.

Immunomodulation with Propionibacterium acnes is used for prophylaxis of respiratory disease or in horses suffering from chronic pulmonary inflammation; however, the mechanism for this response is poorly understood. Semiquantitative reverse transcriptase-polymerase chain reaction assays were used to evaluate gene expression of interleukin (IL)-2, IL-10, interferon (IFN)-gamma, and NK-lysin in healthy horses treated with P. acnes. Findings in the study indicated that horses treated with a P. acnes-based immunomodulator exhibited increased IFN-gamma and NK-lysin gene expression in peripheral blood mononuclear cells. These results suggest that part of the immunostimulating properties of a P. acnes-based immunomodulator is derived from enhanced gene expression of the type-1 cytokine IFN-gamma and NK-lysin, an antimicrobial peptide.

Adjuvants, Immunologic↗

PubMed1992

A sequential multi-assay protocol for the preclinical assessment of natural product complex carbohydrate immunomodulators.

A major barrier to the understanding, development and utilization of natural product complex carbohydrate immunomodulators has been the lack of standardization during pre-clinical efficacy and safety testing. In addition, it has been our experience that no single assay system or model is adequate for assessing preclinical efficacy and safety of these agents. To address these important issues, our laboratory group has developed a sequential multi-assay protocol for the preclinical evaluation of natural product complex carbohydrate immunomodulators. This sequential multi-assay screening protocol is divided into four phases: 1) physiochemical characterization of the carbohydrate polymer; 2) evaluation of immune stimulatory activity; 3) assessing in vivo anti-microbial activity and anti-tumor efficacy and 4) preclinical safety evaluation. This sequential protocol provides an effective, reproducible and rational approach to the preclinical assessment of complex carbohydrate immunomodulators that, in our experience, is predictive of clinical safety and efficacy.

Adjuvants, Immunologic↗

PubMed1992

Evaluation of clinical trials of immunomodulators for prevention of recurrent respiratory infections in children.

Despite numerous clinical studies showing "significant differences" in favour of immunomodulators versus placebo in the treatment and/or prevention of recurrent respiratory tract infections, the efficiency of such treatments is still not readily acknowledged by a large part of the medical profession nor by governmental authorities in several countries. In an effort to analyze the causes of this scepticism we performed a retrospective study of 15 clinical trials, using a series of quality assessment criteria. From the results of our analysis we propose a series of recommendations for improving the quality of clinical trials with immunomodulators. Furthermore, in order to avoid suspicion of a publication bias, we recommend setting up a registry of all ongoing clinical studies with immunomodulators.

Adjuvants, Immunologic↗

PubMedDate not supplied

Immunomodulating effects of the hydrolysis products of formosanin C and beta-ecdysone from Paris formosana Hayata.

Formosanin C (PF-3, I), a diosgenin glycoside with four sugars isolated from Paris formosana Hayata as main constituent, significantly showed immunomodulating effects on the proliferative response of mouse lymphocytes to concanavalin A (Con A). The partialy hydrolysis products of formosanin C, dioscin (II) and prosapogenin A of dioscin (III), also increased 3H-thymidine incorporation of Con A-stimulated lymphocytes maximally at 0.01 micrograms/ml, whereas formosanin C did so at 0.0001 micrograms/ml. However, trillin (IV) and diosgenin (V) obtained from the partial hydrolysis of formosanin C had no effects on these immune responses. Evidently, the immunomodulating activities increased in the order of increasing polarity. Probably the solubility in water was a factor. This demonstrated that the sugar moiety in the structure of formosanin C (I) displays a very important pattern for the effect on the proliferative response of mouse lymphocytes to Con A. On the other hand, these hydrolysis products at higher concentrations of 1 and 10 micrograms/ml reduced the cytotoxic effects on spleen cells as compared with formosanin C. The other constituent, beta-ecdysone (VI) isolated from the stems of Paris formosana Hayata also increased 3H-thymidine incorporation of Con A-stimulated splenocytes. At the concentration of 0.001 micrograms/ml, the stimulation index of beta-ecdysone (2) is higher than that of formosanin C (1.65), and at the concentration of 100 micrograms/ml, beta-ecdysone had no cytotoxicity for normal spleen cells whereas formosanin C at the lower concentration of 10 micrograms/ml showed cytotoxicity. Based on this study, beta-ecdysone (VI) is therefore a better immunomodulator than formosanin C.

Adjuvants, Immunologic↗

PubMedDate not supplied

[Immunomodulation activity of new vaccines for pertussis prophylaxis--acellular pertussis vaccine and adsorbed DPT vaccine with acellular component].

The immunomodulating activity of acellular pertussis vaccine (APV) and adsorbed DPT vaccine with acellular pertussis component (DPTA vaccine) was studied. The study revealed that only large doses of APV, 10 immunizing doses (ID), suppressed humoral and cell-mediated response to sheep red blood cells (SRBC). 1 ID produced no influence on the formation of antibody producing cells, but increased the development of delayed hypersensitivity (DH) to SRBC. The modulation of cell-mediated immune response, induced by APV, returned to normal after the injection of purified staphylococcal toxoid, used as immunomodulator, in doses of 0.15 BU per mouse and 1.5 BU per mouse. DPTA vaccine containing 1 ID, as well as 10 ID, produced no immunomodulating effect. This was established by the evaluation of humoral response to SRBC in CBA mice and the study of the formation of DH to SRBC in BALB/c mice. As indicated by the total of the presented data, the inclusion of APV into DPTA vaccine enhanced the immunological safety of its pertussis component.

Adjuvants, Immunologic↗

PubMedDate not supplied

Topical immunomodulators in dermatology.

Topical immunomodulators are agents that regulate the local immune response of the skin. They are now emerging as the therapy of choice for several immune-mediated dermatoses such as atopic dermatitis, contact allergic dermatitis, alopecia areata, psoriasis, vitiligo, connective tissue disorders such as morphea and lupus erythematosus, disorders of keratinization and several benign and malignant skin tumours, because of their comparable efficacy, ease of application and greater safety than their systemic counterparts. They can be used on a domiciliary basis for longer periods without aggressive monitoring. In this article, we have discussed the mechanism of action, common indications and side-effects of the commonly used topical immunomodulators, excluding topical steroids. Moreover, newer agents, which are still in the experimental stages, have also been described. A MEDLINE search was undertaken using the key words "topical immunomodulators, dermatology" and related articles were also searched. In addition, a manual search for many Indian articles, which are not indexed, was also carried out. Wherever possible, the full article was reviewed. If the full article could not be traced, the abstract was used.

Administration, Topical↗