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 37 records · Page 2Linked to original sources

PubMed1989

Immunomodulators and feeding regulation: a humoral link between the immune and nervous systems.

Cells of the nervous and immune systems have specific receptors for humoral substances that originate in both systems. These elements establish a bidirectional information exchange network between the nervous and immune systems. In particular, neuroregulators (neurotransmitters and neuromodulators) can modulate specific immune system function(s) and immunoregulators (immunomodulators) can modulate specific nervous system function(s). Modulation of immune functions by neuroregulators has been receiving considerable attention; however, modulation of nervous system functions by immunomodulators has been little studied. The presence of immunomodulators in the brain and cerebrospinal fluid may represent local synthesis by astrocytes, microglia, endothelial cells, intrinsic macrophages and blood-derived lymphocytes which cross the blood-brain barrier, or the concentration of substances derived from the peripheral blood. Acute and chronic inflammatory processes, malignancy, and immunological reactions stimulate the synthesis and release of immunomodulators in various cell systems. These immunomodulators have pivotal roles in the coordination of the host defense mechanisms and repair and induce a series of endocrine, metabolic, and neurologic responses. This paper focuses on the effects of immunomodulators (interleukins, tumor necrosis factor, tuftsin, platelet activating factor, and others) on the central nervous system (CNS), in particular, on feeding regulation. It is proposed that an immunomodulatory system regulates food intake by a direct action in the CNS through a specific neuro-immuno interaction. This regulatory system may be operative during acute and chronic disease.

Animals↗

PubMed1991

[Comparative multifactorial analysis of combined administration of injection and peroral forms of an antibiotic with a microbial immunomodulator in experimental anthrax].

Comparative efficacy of the use of injection and oral dosage forms of rifampicin in the subtherapeutic doses in combination with peptidoglycan , an immunomodulator of microbial origin, was studied in respect to experimental anthracic infection with application of multifactorial analysis. It was shown that the antibiotic and immunomodulator had a pronounced synergistic effect. Polynomial statistic models were developed and nomograms or equal level curves defining the survival rate and average life-span (ALS) of the experimental animals within a wide range of the antibiotic and immunomodulator doses and the peptidoglycan dosing time were plotted. The combined use of the injection rifampicin in the subtherapeutic doses and the immunomodulator provided a significant increase in the survival rate and ALS, whereas the use of the oral antibiotic in combination with the immunomodulator increased only the ALS and not the survival rate. Multifactorial analysis proved to be an optimal methodical approach to comparative study of various antibiotic dosage forms used in combination with immunomodulators under experimental conditions.

Adjuvants, Immunologic↗

PubMed1991

[Optimal combined use of rifampicin and immunomodulator of microbial origin in experimental Q-Rickettsia infection].

Multifactorial analysis of the combined use of rifampicin and an immunomodulator of the microbial origin, such as peptidoglycan, was performed on a model of experimental Q fever in albino mice. On the basis of the experimental results, statistic polynomial models describing the weight of the murine spleens and the titers of the complement-binding antibodies were designed. It was shown that the action of the immunomodulator and antibiotic was highly synergistic with respect to the chemotherapeutic activity and antibody titers. The preventive use of the immunomodulator yielded a 30-fold decrease in a rifampicin therapeutic dose. The use of the immunomodulator also provided a pronounced immunomodulating effect with respect to humoral immunity. Nomographs for optimizing the dose-time parameters of the antibacterial and immunomodulating therapy were plotted.

Adjuvants, Immunologic↗

PubMed1986

Immunomodulators and the complement system.

The possible role of immunomodulators in the host-defense mechanism against neoplasm is discussed from the standpoint of the complement system. Serum complement is activated by the majority of immunomodulators in vitro via either the classical or the alternative pathway, and this activation is sometimes observed following systemic administration of immunomodulators. Besides activating the complement, systemic administration of immunomodulators elevates serum complement levels, and in some cases binds complements to tumor cells. Activated serum complement by an immunomodulator induced an accumulation of PMNs in ascites with tumor cell destruction when intraperitoneally injected, indicating that complement-derived chemotactic factors C3a and C5a generated by an immunomodulator had an antitumor effect. This evidence strongly supports the concept that complement system plays an important role in the host-defense mechanism against neoplasm.

Adjuvants, Immunologic↗

PubMed1984

How to find immunomodulators--a look backward and forward.

The history of specific and unspecific immunomodulation is shortly discussed. While repository adjuvants are already established drugs for specific immunomodulation, no unspecific immunomodulator has successfully passed clinical trials in tumor patients yet. As this is in striking contrast to the effects seen with unspecific immunomodulators in experimental immunological and tumor test systems, the value of those screening models to predict clinical success may be asked for. To improve the success rate, it is recommended to test compounds for their immunomodulatory effects as broad as possible in ex vivo and in vivo test systems. Subsequently, the prophylactic as well as therapeutic potency of selected immunomodulating drugs should be evaluated in various models of aptitude, such as chronic infection, autoimmune diseases and chronic inflammatory reactions. Those diseases are at least to a certain extent influenced by the immune system, in contrast to the uncertainty in case of tumour diseases. Screening of immunomodulating compounds in tumor models should be done with special consideration of minimal residual diseases and formation of metastases.

Adjuvants, Immunologic↗

PubMed1992

Determination of the antiinfectious activity of RU 41740 (Biostim) as an example of an immunomodulator.

Evaluation of the anti-infectious activity of an immunomodulator performed either in vitro or in vivo in animals as in humans must answer three questions: what are the targets? what models should be used to study the mechanism of action? what methodology should be selected for the assessment of therapeutic benefit? In the case of RU 41470 (Biostim), an immunomodulator with a known structure and of biological origin affects immunocompetent cells and two essential mediators: II1 and CSF. Because of multiple interactions between anti-infectious, anti-inflammatory and anti-allergic responses, as well as the pleiotropism of mediators, there exists no absolute predictive index of activity in vivo and, independently of models of immune deficiency, experimental infections are a particularly useful pharmacological model for study of the anti-infectious activity of any immunomodulator. In this model, RU 41470 tested by oral, intraperitoneal and aerosol administration, proved to be active regardless of the type of infectious agent for extracellular bacteria, intracellular bacteria, viruses or yeasts. Because of special local features of anti-infectious defences (pulmonary, cutaneous), the target organ must be identified when studying mechanism of action. RU 41740 stimulates the metabolic activities of alveolar macrophage and the target organ is the respiratory tract. From a clinical pharmacology standpoint, stimulation of different immune components has been investigated with RU 41470 at different dosages, using double-blind versus placebo designs. Target pathology, regardless of severity, includes a risk of infection and the existence of an immunological deficiency. Chronic bronchitis is a reference pathology since patients are subject to episodes of infection, resulting in acute decompensation and contributing to worsening of the ventilatory obstructive disorder. Clinical efficacy in terms of anti-infectious prophylaxis must be evaluated by a strict methodological approach: randomized double-blind placebo-controlled trials with prolonged follow-up. RU 41470 is effective in prophylaxis of respiratory infections in chronic bronchitis (reduction in the number of respiratory infections, their duration and in antibiotic consumption) and in prophylaxis of respiratory tract infections in children over one year old. Clinicians faced with the perplexity of the mechanism of action of immunomodulators and their number are preoccupied above all by the response which such an anti-infectious immunomodulator can offer in a context of clinical reality.(ABSTRACT TRUNCATED AT 400 WORDS)

Adjuvants, Immunologic↗

PubMed1996

Oral administration of a bacterial immunomodulator enhances the immune response to cholera toxin.

Attempts to achieve IgA responses in the intestine by oral immunization with non replicating antigens have been characterized by ineffective responses of short duration unless long term dosages are administered. Cholera toxin (CT) is an exception in that it is able to produce a high secretory and systemic immune response. We study the effects of a bacterial immunomodulator [3 x 10(10) Propionibacterium granulosum ml-1 and lipopolysaccharide (LPS) 5 mg ml-1] on the immune response to CT orally administered to Wistar rats. The immunomodulator was orally administered as follows: in schedule 1 during 7 days prior to the first dose of CT; and in schedule 2, 2 days before, together, and 3 days after the first dose of CT. Schedules 1 and 2 were effective in increasing the specific IgA in the intestinal fluid and specific IgG in serum (P < 0.001) when compared to controls. Besides, schedule 2 was more effective than schedule 1 when the levels of specific IgG in serum or specific IgA in intestinal fluid was measured (P < 0.05). Total IgA in the intestinal fluid was increased in rats receiving the immunomodulator (P < 0.01). However, the ratio of specific IgA per total IgA was higher in rats receiving treatment 1 or 2 when compared to controls (P < 0.01). The number of antitoxin antibody producing cells was not increased in the Peyer patches, but a significant increase was observed in the mesenteric lymph nodes and spleen when compared to controls (P < 0.05). The administration of LPS alone produced an increase in the antitoxin immune response when compared to controls, but it was lower than those produced by the administration of the immunomodulator. These results indicate that this immunomodulator is an effective adjuvant of the mucosal and systemic immune response to CT. The mechanisms of action possibly involve nonespecific and specific modulations of the immune response.

Adjuvants, Immunologic↗

PubMed1990

Model systems to study immunomodulation in domestic food animals.

Development of immunomodulators for use in food producing animals is an active area of research. This research has generally incorporated aspects of immunosuppression in model systems. This methodology is appropriate because most of the research has been aimed at developing immunomodulators for certain economically significant diseases in which immunosuppression is believed to be an important component of their pathogenesis. The primary focus has been on stress-associated diseases (especially bovine respiratory disease), infectious diseases in young animals, and mastitis. The model systems used have limitations, but they have demonstrated that immunomodulators are capable of significantly increasing resistance to these important infectious disease syndromes. As our understanding of molecular immunology increases and as more potential immunomodulators become available, the use of relevant model systems should greatly aid advancement in the field of immunomodulation.

Animals↗

PubMed2001

Immunomodulators for prevention and treatment of infectious diseases in food-producing animals.

The goal of immunomodulation in food-producing animals is to regulate immunity for the benefit of the animal and production efficiency. Immunomodulators are substances that exert this control and include cytokines, pharmaceuticals, microbial products, nutraceuticals, and traditional medicinal plants. Although treatment and prevention of infectious diseases are the most common reasons to use immunomodulators, other conditions, such as amelioration of stress-induced immunosuppression, maturation of the neonate's developing immune response, and strategies to reduce the metabolic cost of eliciting an immune response also are well suited for immunomodulation. Continued discovery of new immune regulators and increased understanding of immunity in food-producing animals will ensure new opportunities for the use of immunomodulators in food-producing animals.

Adjuvants, Immunologic↗

PubMed2003

Is immunomodulation by opioid drugs of clinical relevance?

PURPOSE OF REVIEW: There has been a growing interest in elucidating the immune consequences of opioid administration for the management of pain. Several studies in vitro and in vivo have demonstrated an immunomodulating effect of opioids. The neuro-endocrine interactions observed after opioid application contribute to this effect as well as direct alterations of immune effector cells. Opioid-induced immunomodulation is mediated by opioid receptors found on immunocytes and in the central nervous system. This review will elucidate the molecular mechanisms of central and peripheral immunomodulation by opioids with special emphasis on the clinical significance of these findings. RECENT FINDINGS: Recent research has focused on the cellular signaling cascades associated with opioid receptor activation. The crosstalk between chemokine and opioid receptors on leukocytes has opened new insights into the molecular mechanisms involved in opioid-induced immunomodulation. Heterologous desensitization and phosphorylation of chemokine receptors by opioids may not only mediate the immunosuppressive effects of opioids but may also modulate the perception of pain. SUMMARY: Although immunomodulating effects of opioids are well established, a final statement regarding the clinical relevance cannot be made, since the existing clinical and experimental data are preliminary and inconclusive. Therefore, further clinical studies are mandatory to elucidate the influence of opioid treatment on immune regulation in different clinical settings. Further investigations may help to provide sufficient analgesia by application of opioids, as well as assessing the advantages and disadvantages on immune function.

Journal Article↗

PubMed1997

CD28-B7 T-cell co-stimulatory blockade potentiates the effects of intrathymic immunomodulation in sensitized graft recipients.

BACKGROUND: Peripheral and central immune mechanisms contribute to the induction of tolerance in acute rejection rodent transplant models after systemic administration of CTLA4Ig and intrathymic infusion of donor alloantigen, respectively. We have investigated the effects of CTLA4Ig-induced blockade of CD28-B7 T-cell co-stimulation in conjunction with intrathymic immunomodulation on cellular and humoral immune responses leading to accelerated rejection of cardiac allografts in presensitized rats. METHODS AND RESULTS: Lewis rats were challenged with Wistar-Furth (WF) skin transplants, followed 7 days later by transplantation of WF hearts. These cardiac allografts were rejected in a fulminant manner in <24 hr. A single infusion of human CTLA4Ig (0.5 mg/rat i.v.) at the time of cardiac engraftment (day 0) did not affect accelerated rejection. Intrathymic injection of WF spleen cells (2x10[7]) at the time of skin transplantation (day -7) abrogated <24-hr rejection and extended cardiac allograft survival to 6.6+/-0.6 days. Moreover, intrathymic host immunomodulation combined with administration of human CTLA4Ig (days 0-14, every other day) extended cardiac allograft survival synergistically to 27.7+/-7.5 days, and immunomodulation combined with murine CTLA4Ig extended survival to >42.5+/-4.8 days. The prolongation of allograft survival required the blockade of both B7-1 and B7-2 ligands and was accompanied by reduction of host proliferative responses (mixed lymphocyte response) and depression of anti-donor cytotoxic T-cell generation/function (lymphocyte-mediated cytotoxicity). CTLA4Ig therapy did not affect the strong systemic IgM and IgG alloantibody response seen otherwise after intrathymic immunomodulation. CONCLUSION: CTLA4Ig enhances the effects of intrathymic donor-type cell infusion in sensitized rat recipients of cardiac allografts, indicating that "peripheral" blockade of CD28-B7 T-cell co-stimulation synergizes with the "central" immunosuppressive effects of intrathymic immunomodulation.

Abatacept↗

PubMed2004

Smoking and immunomodulators do not influence the response or duration of response to infliximab in Crohn's disease.

OBJECTIVE: Clinical predictors for infliximab response are still unknown. Identifying predictors of response to infliximab in Crohn's disease may improve our selection of patients. METHODS: Two hundred patients with luminal (61%) or fistulous (39%) Crohn's disease and at least 6 months of follow-up following a total of 416 infliximab infusions were evaluated. Clinical response and duration of response were the primary endpoints. RESULTS: Patients with fistulous disease had a higher response rate (83% versus 70%, P = 0.044) and a significantly longer duration of response compared with patients with luminal disease (17.4 versus 10.1 wks, P = 0.017). For luminal disease, nonsmokers and smokers had similar response rates (74% versus 64%, P = 0.5) and similar durations of response (9.4 wks versus 8.4 wks P = 0.6) while patients taking concurrent immunomodulators had similar response rates compared with those not taking immunomodulators (74% versus 71%, P = 0.9) and similar durations of response (10.4 wks versus 10.6 wks, P = 0.9). For fistulous disease, response rates (89% versus 83% P = 0.9) and duration of response (16.9 wks versus 10.1 wks, P = 0.10) were similar between nonsmokers and smokers and concurrent immunomodulators had no effect on response (89% versus 86%, P = 0.9) or duration of response (19.8 wks versus 15.4 wks, P = 0.46). Multivariable analysis confirmed that neither smoking, corticosteroids, immunomodulator therapy, gender, age, age of disease onset, disease duration, nor luminal disease location significantly influenced response or duration of response. CONCLUSIONS: Patients with fistulous disease had a higher response rate and a significantly longer duration of response compared with patients with luminal disease. However, among patients with luminal or fistulous disease, neither smoking nor immunomodulators had any effect on response or duration of response.

Adjuvants, Immunologic↗

PubMed2001

Immunomodulating anticancer alkylating drugs: targets and mechanisms of activity.

CY and L-PAM potentiated specific anti-tumor response in addition to their killing effect. The immunomodulating effect of a low dose of either CY or L-PAM was expressed in mice bearing large s.c. MOPC-315 plasmacytoma tumors. Cured mice were resistant to a challenge dose of the syngeneic tumor and their spleens contained specific cytotoxic T cells. Induction of specific anti-tumor response by a low dose of alkylating drugs was due to expression of "latent anti-tumor" capability. This fitted with the conception that "suppressed concomitant immunity" occurring in tumor-bearing animals can be activated. The immunomodulating activity of alkylating drugs was related to enhancement of T-cell functions:impairment of suppressor T-cell activity,enhancement of effector T-cell activity and increase in production of cytokines at the tumor site. The target tumor killing activity of a low dose alkylating drug was dissociated from its immunomodulating activity by treating mice bearing a tumor resistant to an alkylating drug. A low dose of CY had an immunomodulating effect in human cancer such as reduction of ConA-induced suppressor cell activity in melanoma, some improvement in addition to use of melanoma vaccine, and potentiation of DTH in cancer patients. The immunomodulating effect of alkylating drugs suggest that their use might be beneficial not only for killing tumor cells but also for promoting specific anti-tumor immune response.

Adjuvants, Immunologic↗

PubMed2001

Immunomodulating mechanisms in the lower respiratory tract: nitric oxide mediated interactions between alveolar macrophages, epithelial cells, and T-cells.

A number of immunomodulating mechanisms are necessary to prevent uncontrolled inflammation in the lower respiratory tract. Proliferative responses of immune cells are tightly controlled in both bronchi and alveoli in the healthy lung. In diseases such as bronchial asthma, there is not only a partial failure of these mechanisms, but also an immune-deviation with a propensity towards a Th2-cell involvement. The role of alveolar macrophages (AM) controlling T- and B-cell activation in the lower respiratory tract is discussed by considering mainly published results. This review focuses on immunomodulating mechanisms exerted via cytokines, such as Interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), and Interleukin-1 receptor-antagonist (IL-1ra), prostaglandins, such as prostaglandin E2 (PGE2), and especially nitric oxide (NO). The Th1 and Th2 concept in asthma is introduced, being the best-described mechanism of immune-deviation in the lung. The possibility of re-inducing T-cell unresponsiveness is of particular interest. The physiological immunomodulating mechanisms used by AM are explained in detail, as they offer many possibilities for therapeutic immunomodulation. Special emphasis is put on the cGMP/phosphatase dependent, reversible mechanism of NO-mediated immunomodulation and differences in the activation of NO synthases between murine and human alveolar macrophages are mentioned.

Animals↗

PubMedDate not supplied

In vitro response of phagocytic cells to immunomodulating agents.

BACKGROUND: Phagocytes (polymorphonuclear cells and monocyte-macrophages) are the first line of defence of the host against infectious microorganisms and other foreign antigens. Agents which participate in activation of phagocytic cells possess a potential immunomodulating action. Thus, search for convenient in vitro test-systems and study of mechanisms of action of these agents are of practical interest. MATERIAL AND METHODS: Human blood polymorphonuclear (PMN) cells and murine macrophages (line J774.2) were used as cellular test-systems for study of phagocytosis-stimulating action of immunomodulating agents. Indexes of phagocytic activity were estimated by the phagocyte ingestion of yeast cells. NO-synthase activity, nitrite production, and nitroblue tetrazolium test were determined after phagocyte stimulation. RESULTS: It was revealed that indexes of phagocytic activity can be used as quantitative indicators for measurement immunomodulating activity. Zymosan A-induced phagocytosis in almost 100% PMN cells and macrophages and thus can be used as a positive control. Wheat germ agglutinin (WGA, 0.5-1.0 microg/ml) stimulated phagocytosis in PMN cells 1.8 times after 2-3 h incubation, although in higher concentrations (5-10 microg/ml) it strongly inhibited phagocytosis. TGF-b1 (10 ng/ml) suppressed phagocytosis in WGA-stimulated PMN cells. Mistletoe agglutinin-1 stimulated phagocytosis in PMN cells, although its effect in macrophages was weak, while concanavalin A stimulation of phagocytosis in macrophages was well expressed. Vasodilating peptide bradykinin increased phagocytosis 2.5 times in macrophages. We did not reveal changes in NO-synthase activity and nitrite production in macrophages and PMN cells activated by different immunomodulatig agents. Only lipopolysacharide stimulated such activity in macrophages. CONCLUSIONS: Cultured macrophages and PMN cells can provide reproducible quantitative results in screening phagocytic activity of different immunomodulating agents. Both positively and negatively acting immunomodulators might be studied using these test cells.

Adjuvants, Immunologic↗

PubMed2002

Effect of an immunomodulator containing Mycobacterium w on sputum conversion in pulmonary tuberculosis.

Sputum conversion is an important milestone in the management of pulmonary tuberculosis. Early sputum conversion is desirable. A controlled study was done to improve sputum conversion rate of current short course chemotherapy using immunomodulator containing mycobacterium w. The immunomodulator is very potent and freely available. It shares antigens with Mycobacterium tuberculosis. In a randomised pattern 69 of 134 patients suffering from pulmonary tuberculosis received the immunomodulator intradermally every 15 days along with chemotherapy. The use of the immunomodulator results in preponement of sputum conversion. The sputum conversion rate obtained by chemotherapy at 60 days was achieved latest by 30 days when mycobacterium w containing immunomodulator was used as an adjuvant therapy. This was found irrespective of bacterial load (1 +, minimal or 3+, maximal) in sputum or category (fresh or retreatment) of disease. The therapy was well tolerated.

Adjuvants, Immunologic↗

PubMed1992

[Combined experimental use of vaccine against acute human encephalomyelitis and immunomodulators].

Combined use of vaccine and immunomodulators such as ridostin, inosiplex and polyribonate against acute encephalomyelitis of humans (AEMHs) was studied. It was shown that low immunogenic doses of the vaccine did not provide a protective action against the virus of AEMHs while after administration of the vaccine in combination with the immunomodulators there was protection in all the groups of the animals exposed to the low immunogenic doses of the vaccine during the first immunization. It was noted in regard to all the combinations of the immunomodulators and vaccine used in the low immunogenic doses that the level of the increase in the titer of the virus-specific antibodies, the proliferative activity to the specific antigen and mitogens and of interferon induction depended on the immunomodulator type. At the same time, it was found that the marked production of interferon within the first 24 hours observed after the use of the combination of inosiplex, ridostin and the vaccine resulted in increased activity of natural killer cells and lower proliferative activity of cells and production of virus-specific antibodies. This was indicative of the necessity of choosing the immunomodulators, their doses and time of the administration in relation to the immunization.

Acute Disease↗

PubMed1992

Evaluation of assay procedures measuring macrophage stimulation by immunomodulators in vitro.

Several assay procedures for measuring the stimulatory effect on macrophages (møs) of bacterial-derived immunomodulators (OM-85, OM-89, OM-163, Laboratoires OM, Meyrin/Geneva, Switzerland) were evaluated with regard to their complexity, speed, and general convenience. To this effect, bone marrow-derived or peritoneal exudate macrophages were exposed to the immunomodulators in vitro, then tested for metabolic stimulation (glucose oxidation through the hexosemonophosphate shunt pathway, synthesis of type E prostaglandins, release of superoxide, and production of L-arginine-derived nitrogen oxidation products), as well as for enhancement of functional activities (production of tumor necrosis factor-alpha, extracellular cytolysis of P815 target cells, and intracellular parasite destruction). All these tests were found to provide adequate measurements of the mø response to the immunomodulators, with significant effects detectable using the compounds in the ng/ml to microgram/ml range. Concomitant incubation with crude macrophage activating factor or with recombinant murine interferon-gamma (IFN-gamma) dramatically increased the sensitivity of møs to the immunomodulators, and was an absolute requirement for induction of mø cytotoxic activities by the bacterial extracts. The measurement of nitrite production by møs exposed to the immunomodulators with or without treatment with 10 U/ml of IFN-gamma was found to be a highly convenient procedure, which correlated well with functional assays.

Adjuvants, Immunologic↗