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Results for “immunomodulation”

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At least 145 records · Page 8Linked to original sources

PubMed2003

Leflunomide treatment of Crohn's disease patients intolerant to standard immunomodulator therapy.

BACKGROUND: Immunomodulator therapy with the purine analogs azathioprine and 6-mercaptopurine (6-MP), is efficacious in the treatment of moderate to severe Crohn's disease (CD), but is not tolerated by a significant minority of patients. The pyrimidine analog, leflunomide, has demonstrated efficacy in the treatment of rheumatoid arthritis (RA) patients. Because established RA immunomodulator agents may demonstrate success in the treatment of CD, we reviewed our clinical open-label experience with leflunomide in a refractory CD population. GOALS Assess the effect of leflunomide 20 mg daily, on disease activity, steroid requirement and serologic measures of inflammatory activity in our series of CD patients intolerant to azathioprine/6-MP. STUDY: CD patients intolerant of azathioprine/6-MP were offered leflunomide treatment. The Harvey-Bradshaw (H-B) disease activity index, global assessment, serologic parameters and ability to taper corticosteroids of those who accepted were retrospectively assessed. RESULTS: Leflunomide was well tolerated and resulted in a significant reduction in the H-B score, global assessment and serologic parameters in 8/12 patients. Average follow-up was 38 weeks and a majority of steroid-dependent patients were able to successfully taper following leflunomide initiation. CONCLUSIONS: Our case series demonstrates that the pyrimidine analog leflunomide may be effective for treating moderate to severe CD patients intolerant to standard immunomodulator therapy and warrants further investigation in a randomized controlled trial.

Adjuvants, Immunologic↗

PubMed1987

Immunomodulators and wound healing.

The synthetic immunomodulators muramyl dipeptide (MDP), thymopoietin pentapeptide (TP5), and CP-46,665 were examined for their effects on wound healing in mice. We found no differences in wound disruption strength between immunomodulator-treated animals and saline controls on days 11, 14, and 21. The only exception was with high-dose CP-46,665, which produced weakened wounds on day 14 (p less than 0.05) and 21 (p less than 0.01). CP-46,665 was further studied by injecting high and low doses 48 hours before or after wounding. No differences were seen for these groups compared to controls at 11 and 21 days. Finally, to simulate a common clinical situation, mice were subjected to a 10% total body surface area (TBSA) burn to the right paraspinal region. Twenty-four hours later, a left paraspinal incision was performed with simultaneous injection of saline, Corynebacterium parvum (C. parvum), or low-dose TP-5, MDP, or CP-46,665. At 11 days, no detriment in wound healing was found for burned control or any of the immunomodulator-treated animals except in the C. parvum-treated mice, with significantly weakened skin strips (p less than 0.001). While C. parvum may be detrimental to wound healing, the synthetic modulators tested appear to have little effect on wound healing.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1999

Effects of immunomodulation with interferon-gamma on hepatic ischemia-reperfusion injury.

The development of an inflammatory response after injury depends on the participation of a variety of cell populations and endogenous mediators. Interferon-gamma (IFN-gamma) is a potent cellular immunomodulating cytokine that contributes to acute and chronic inflammation. In this study, the effects of immunomodulation on ischemia-reperfusion injury were examined using increasing doses of recombinant, rabbit-specific IFN-gamma in an in situ model of hepatic ischemia-reperfusion. Pretreatment with low dose IFN-gamma augmented injury as measured by histology, aminotransferase concentrations, and myeloperoxidase activity. By contrast, high dose IFN-gamma pretreatment, equivalent to IFN-gamma supplements used in clinical trials, resulted in a lack of neutrophil infiltration and minimal progression of late phase, neutrophil-mediated reperfusion injury. These results suggest that immunomodulating mediators such as IFN-gamma may play a regulating role in the evolution of ischemia-reperfusion, contributing to the development and resolution of acute hepatic injury.

Adjuvants, Immunologic↗

PubMed2006

Remission on thiopurinic immunomodulators normalizes quality of life and psychological status in patients with Crohn's disease.

BACKGROUND: Thiopurinic immunomodulators are effective for maintaining symptom remission in Crohn's disease. Little is known, however, about their effect on patients' quality of life or psychological well-being. The present study aimed to determine whether remission induced by thiopurinic immunomodulators returns levels of quality of life and psychological well-being to normal. MATERIALS AND METHODS: A case-control study was performed. Cases were 33 patients with Crohn's disease treated with azathioprine or 6-mercaptopurine and in stable remission for at least 6 months. Sixty-six healthy individuals matched 2:1 by age and sex and 14 patients with active Crohn's disease were included as control groups. Quality of life was evaluated with the Short Form (SF-36) questionnaire, and the respective Hamilton rating scales were used for anxiety and depression. ANOVA with Bonferroni's correction was used for multiple comparisons. RESULTS: SF-36 global scores were 85 in the study group, 85 in healthy controls (P = 1), and 58.6 in patients with active disease (P < 0.001 for the comparison with the other 2 groups). The differences between values were 0 (95% CI -4-4), 26.4 (95% CI 20-32), and 26.4 (95% CI 19-33), respectively. The respective anxiety and depression scores were 6.5, 5.5, and 16.2 and 3.7, 3.3, and 10.9. No significant differences were observed in any of the SF-36 domains between case and control groups, whereas in patients with active disease, all domains were significantly worse. CONCLUSIONS: Thiopurinic immunomodulator-induced remission restores normal levels of quality of life and psychological well-being in Crohn's disease patients.

Adult↗

PubMed2004

Efficacy and safety of thiopurinic immunomodulators (azathioprine and mercaptopurine) in steroid-dependent ulcerative colitis.

BACKGROUND: The efficacy of azathioprine in the management of steroid-dependent ulcerative colitis is taken for granted. However, study populations frequently include together steroid-dependent and refractory patients. AIM: To assess the efficacy and safety of thiopurinic immunomodulators in strictly defined steroid-dependent ulcerative colitis. METHODS: Survey of 34 patients with steroid-dependent ulcerative colitis, treated with azathioprine according to protocol. Therapeutical success: glucocorticoid withdrawal within 12 months, without steroid requirements during another year. RESULTS: Mean age was 39.1 +/- 17 years. Pancolitis and extensive colitis accounted for 50% of cases. Therapeutic success of immunomodulator treatment reached 70.6%, intention to treat analysis (confidence interval 95%: 52-84%) and 72.7%, as per protocol (confidence interval 95%: 54-86%). Mean time to steroid withdrawal was 4.6 months. In therapy successes, mean corpuscular volume and total serum bilirubin increased with treatment time (P = 0.0001). Fifteen adverse effects were observed in 13 patients (38%). Azathioprine was withdrawn in seven cases (20.6%); in four of them (with liver toxicity), treatment with mercaptopurine was indicated. CONCLUSIONS: Therapy with thiopurinic immunomodulators (azathioprine) represents the first option in the management of steroid-dependent ulcerative colitis. Its efficacy (70%) and its acceptable safety support this view. Increasing mean corpuscular volume and serum bilirubin values may be a surrogate marker of a beneficial effect.

Adult↗

PubMed2005

Review article: monitoring of immunomodulators in inflammatory bowel disease.

The armamentarium of medications for the treatment of inflammatory bowel disease is growing and becoming more complicated to use. Immunomodulators are a class of medications that have found a niche for the treatment of Crohn's disease and ulcerative colitis. Because of the mounting supporting evidence for efficacy, the most commonly-used immunomodulators are azathioprine, mercaptopurine, methotrexate and ciclosporin. These medications are being used more often due to their steroid-sparing and potentially surgery-sparing effects. Immunomodulators are also known for a significant side-effect profile and require careful monitoring. This review provides the latest information for clinicians on efficacy, side-effects, dosing and monitoring of these medications for treatment of inflammatory bowel disease.

Azathioprine↗

PubMed2005

Review article: practical management of inflammatory bowel disease patients taking immunomodulators.

Azathioprine, mercaptopurine, methotrexate, ciclosporin and tacrolimus all have their respective niches in the treatment of inflammatory bowel disease. These immunomodulators are potent and effective medications; however, they potentially have serious toxicity. To maximize benefit and minimize risk, clinicians must understand the mechanism of action, appropriate indications, range of toxicity and proper dosing of these medications. Furthermore, once initiating therapy, patients need to be monitored appropriately for evidence of efficacy and toxicity. This review includes the rationale behind recommendations for the management and monitoring of patients using immunomodulators. For the purine antagonists--azathioprine and mercaptopurine--the evidence for utility of thiopurine methyltransferase testing and mercaptopurine metabolite monitoring is addressed. The roles of liver biopsy and screening for methylenetetrahydrofolate reductase mutations in patients taking methotrexate are reviewed. With appropriate monitoring, the calcineurin inhibitors--ciclosporin and tacrolimus--can be used safely and effectively. Immunomodulators are important agents for the treatment of Crohn's disease and ulcerative colitis, and prescribing clinicians should be comfortable recognizing both their value and their limitations.

Dose-Response Relationship, Drug↗

PubMed2004

Immunomodulation by roquinimex decreases the expression of IL-23 (p19) mRNA in the brains of herpes simplex virus type 1 infected BALB/c mice.

Herpes simplex virus (HSV) is a common neurotropic virus which infects epithelial cells and subsequently the trigeminal ganglia (TG) and brain tissue. We studied how immunomodulation with roquinimex (Linomide) affects the course of corneal HSV infection in BALB/c mice. BALB/c mice have also been used in a model for HSV-based vectors in treating an autoimmune disease of the central nervous system (CNS). We addressed the questions of how immunomodulation affects the local as well as the systemic immune response and whether roquinimex could facilitate the spread of HSV to the CNS. The cytokine response in the brain and TG was studied using a quantitative rapid real-time RT-PCR method. We were interested in whether immunomodulation affects the expression of the recently described Th1-cytokine IL-23p19 in the brain and TG. The expression of IL-23 mRNA was decreased in brains of roquinimex-treated BALB/c mice. Also the expression of IL-12p35 and IFN-gamma mRNAs decreased. No significant changes were seen in IL-4 and IL-10 mRNA expression. The cytokine response was also studied using supernatants of stimulated splenocytes by EIA. Roquinimex treatment suppressed the production of IFN-gamma and also the production of IL-10 in HSV-infected BALB/c mice.

Adjuvants, Immunologic↗

PubMed2006

Immunomodulation of the hepatic egg granuloma in Schistosoma japonicum-infected pigs.

Immunomodulation of perioval granulomas is a well-known phenomenon in schistosome-infected mice, but only little is known about granuloma modulation in other animal models of human schistosomiasis. In the present study, we explored immunomodulation of egg granulomas in the liver in a pig model of schistosomiasis japonica. Granuloma size was measured and T cells, B cells and IgG(+) plasma cells in granulomas were quantified in pigs at 9, 12 and 21 weeks post infection (wpi) with Schistosoma japonicum. Granulomas were largest at 9 wpi, had decreased significantly in size at 12 wpi and remained small at 21 wpi (9 vs. 12 and 21 wpi: P < 0.05). The size of granulomas containing mature and immature eggs, respectively, did not differ significantly. The density of T (CD3epsilon(+)) cells and IgG(+) plasma cells in granulomas was the same, irrespective of granuloma size and time points. B (CD79alpha(+)) cells were rare in granulomas. The results indicate that in pigs, S. japonicum egg granulomas in the liver are immunomodulated at an early stage of infection, and that not only mature but also immature eggs induce a marked granulomatous reaction in this species.

Animals↗

PubMed1992

Effects of immunomodulators on ecto-5'-nucleotidase activity on blood mononuclear cells in vitro.

In this study the effects of immunomodulators on the ecto-5'-nucleotidase (ecto-5'-NT) activity on blood mononuclear cells (BMC) were examined in vitro. Interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) decreased the level of ecto-5'-NT activity on BMC whereas prostaglandin E2 (PGE2) increased the ecto-5'-NT level. All three immunomodulators influenced the ecto-5'-NT activity of isolated monocytes whereas only IL-4 and PGE2 had an effect on the enzyme level on isolated lymphocytes. The effect was dependent upon protein synthesis. The effect was dose dependent: IL-4 was effective at concentrations down to 0.5 U/ml, IFN-gamma down to 40 U/ml and PGE2 at nanomolar concentrations. These data indicate that immunomodulators may also take part in the regulation of ecto-5'-NT activity on BMC in vivo. BMC from 7 patients with different immunodeficiency syndromes showed decreased ecto-5'-NT activity on freshly isolated cells. However, following culture ecto-5'-NT activity was increased above the level found on freshly isolated BMC from healthy persons. On BMC from 3 patients with hypogammaglobulinaemia, the effect of IL-4 on the level of ecto-5'-NT activity was identical to that found on BMC from healthy donors, whereas PGE2 increased ecto-5'-NT activity on BMC from only 1 of the 3 patients investigated. The decreased ecto-5'-NT activity of BMC from patients with immunodeficiency may thus be due to a defective regulation of ecto-5'-NT activity in vivo.

5'-Nucleotidase↗

PubMed2004

Immunomodulation and immunodeficiency.

This article briefly reviews the concepts of immunodeficiency and immunomodulation as they relate to selected skin diseases in the dog and cat. Immunodeficiency states are uncommon and may be associated with a subnormal or down-regulated immune system, including humoral deficiencies, such as IgA, and abnormal lymphocyte or neutrophil function. Establishing a causal relationship between a skin disease and presumed immunodeficient state has been difficult due to the rarity of such conditions, and the limited nature of the techniques used to characterise the immune system response. Severe combined immunodeficiency in dogs is a well characterised primary immunodeficiency state involving lymphocytes; retrovirus infection in cats may lead to an acquired immunodeficient state with some association with certain dermatological conditions although it remains unclear that infection is causally linked with disease. Immunomodulation usually implies stimulating the immune system along a beneficial pathway. Such a therapeutic approach may involve a wide variety of agents, for example intravenous immunoglobulin. There are few randomised controlled trials with veterinary patients that unequivocally demonstrate beneficial responses to immunomodulatory agents. Interferons are cytokines of major interest in human and veterinary medicine for their antiviral, anti-tumour and immunomodulatory effects. The advent of veterinary-licensed products containing recombinant interferon may enable demonstration of the efficacy of interferons for conditions such as canine papillomatosis and feline eosinophilic granuloma complex. Canine pyoderma has been treated with a number of presumed immunomodulatory agents with limited success. With more detailed knowledge of the pathogenesis of pyoderma it may be possible to develop efficacious immunomodulators.

Adjuvants, Immunologic↗

PubMed1986

Immunomodulation: bioengineering aspects.

Plasmapheresis is generally recognized as a "black box" therapy. Factors effecting the immunomodulating influence of plasmapheresis and their impact on the clinical results include the disease state and stage, associated drug and medical therapies, and the methodology of plasmapheresis. The immunomodulating influence of the methodology of plasmapheresis, including duration of treatment, frequency of treatment, equipment type, materials choice, anticoagulant choice, and volume replacement versus selective removal, has a profound impact on the clinical results. Limitations in the design of controlled trials emphasize the importance of assessing the events occurring within and as a result of the individual black box utilized in plasmapheresis therapy. The analysis and understanding of the immunomodulating influences of the "black box" will prove to be very valuable in the development of better technologies for patient care.

Biocompatible Materials↗

PubMed1992

Potential role of immunomodulators for treatment of phlebovirus infections of animals.

Rift Valley fever (RVFV) is a major phlebovirus-induced epizootic disease of domestic animals (primarily cattle and sheep) in Africa. No therapies for the disease are known. A related phlebovirus, Punta Toro virus (PTV), has been adapted to induce an RVFV-like disease in C57BL/6 mice. This PTV infection has been used as a model for RVFV because it is reasonably safe and does not require high-level biologic containment. The infection model has been used to study the potential role of immunomodulating substances as therapies. A spectrum of immunomodulators has been studied; those immunomodulators most capable of preventing death and other disease manifestations are ampligen, bropirimine, poly (ICLC), AM-3, P-136, and 7-thia-8-oxoguanosine. An immunologic parameter common to all these substances has been their ability to induce interferon. Timing studies have indicated that these active substances may be administered therapeutically as well as prophylactically to inhibit markedly the progress of the disease. Further work is needed in the development of these materials for use in treating viral infections in domestic animals. As a next step, studies need to be run to compare the immunologic profiles induced by each substance in domestic animals and in mice.

Adjuvants, Immunologic↗

PubMed1993

Immunomodulator effects on the Friend virus infection in genetically defined mice.

The disease induced by the Friend virus complex (FV) in F1 hybrid mice containing the Rfv-3r/s genotype in the presence of H-2a/a was used to evaluate a variety of immunomodulating substances. In these genetically defined mice, the FV disease results in splenomegaly, early production of high titers of cell-associated and plasma virus, high levels of splenic viral RNA, increased hematocrit, and eventual death. As the disease progresses, reduced levels of infectious virus correlate with development of specific antibody; reduction in T cell populations, increase in B cells, and decrease in T-cell function also occur. The following immunomodulators were evaluated, listed in the order of their ability to inhibit the FV disease: imexon > MVE-2 > human recombinant IFN-alpha A/D > AS101 > ampligen > AM-3 = oxamisole > ImuVert > bropirimine. In fact, bropirimine, used with certain treatment regimens, appeared to enhance the FV disease. These data suggest that certain immunomodulators may have potential value in the treatment of HIV disease, but also indicate that caution should be exercised in their clinical use.

Adjuvants, Immunologic↗

PubMed2000

Polysaccharide immunomodulators as therapeutic agents: structural aspects and biologic function.

Polysaccharide immunomodulators were first discovered over 40 years ago. Although very few have been rigorously studied, recent reports have revealed the mechanism of action and structure-function attributes of some of these molecules. Certain polysaccharide immunomodulators have been identified that have profound effects in the regulation of immune responses during the progression of infectious diseases, and studies have begun to define structural aspects of these molecules that govern their function and interaction with cells of the host immune system. These polymers can influence innate and cell-mediated immunity through interactions with T cells, monocytes, macrophages, and polymorphonuclear lymphocytes. The ability to modulate the immune response in an appropriate way can enhance the host's immune response to certain infections. In addition, this strategy can be utilized to augment current treatment regimens such as antimicrobial therapy that are becoming less efficacious with the advent of antibiotic resistance. This review focuses on recent studies that illustrate the structural and biologic activities of specific polysaccharide immunomodulators and outlines their potential for clinical use.

Adjuvants, Immunologic↗

PubMed2001

Selective regulation of human immunodeficiency virus-infected CD4(+) lymphocytes by a synthetic immunomodulator leads to potent virus suppression in vitro and in hu-PBL-SCID mice.

We have previously observed that the synthetic immunomodulator Murabutide inhibits human immunodeficiency virus type 1 (HIV-1) replication at multiple levels in macrophages and dendritic cells. The present study was designed to profile the activity of Murabutide on CD8-depleted phytohemagglutinin-activated lymphocytes from HIV-1-infected subjects and on the outcome of HIV-1 infection in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice). Maintaining cultures of CD8-depleted blasts from 36 patients in the presence of Murabutide produced dramatically reduced levels of viral p24 protein in the supernatants. This activity correlated with reduced viral transcripts and proviral DNA, was evident in cultures harboring R5, X4-R5, or X4 HIV-1 isolates, was not linked to inhibition of cellular DNA synthesis, and did not correlate with beta-chemokine release. Moreover, c-myc mRNA expression was down-regulated in Murabutide-treated cells, suggesting potential interference of the immunomodulator with the nuclear transport of viral preintegration complexes. On the other hand, daily treatment of HIV-1-infected hu-PBL-SCID mice with Murabutide significantly reduced the viral loads in plasma and the proviral DNA content in human peritoneal cells. These results are the first to demonstrate that a clinically acceptable synthetic immunomodulator with an ability to enhance the host's nonspecific immune defense mechanisms against infections can directly regulate cellular factors in infected lymphocytes, leading to controlled HIV-1 replication.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2004

Immunomodulating effects of "tien-hsien liquid" on peripheral blood mononuclear cells and T-lymphocytes from patients with recurrent aphthous ulcerations.

Recurrent aphthous ulcerations (RAU) represent a common oral mucosal disease with altered humoral and cellular immunities. In our institution, an immunomodulating agent, levamisole, is used to treat RAU with satisfactory therapeutic effect. Tien-Hsien liquid (THL) is an extract of Chinese medicinal herbs with immunomodulating effects. To test whether THL has immunomodulating effects on antigen-stimulated proliferation response (PR) of peripheral blood mononuclear cells (PBMC) and T-cells isolated from RAU patients and to test whether THL is a potential drug for treating RAU, PBMC or T-cells isolated from RAU patients were incubated with lipopolysaccharides (LPS) from Escherica coli, phytohemagglutinin (PHA), staphylococcal enterotoxin B (SEB), glutaraldehyde-inactivated tetanus toxoid (TT), glucosyltransferase D (GtfD), or antigens of Streptococcus mutans in the presence or absence of THL. We found that THL significantly increased the LPS-stimulated PR of PBMC from active RAU patients, the GtfD-stimulated PR of PBMC and of T-cells from inactive RAU patients, and the S. mutans-stimulated PR of PBMC from inactive RAU patients. However, THL could also significantly reduce the SEB-stimulated PR of PBMC and of T-cells from active RAU patients and S. mutans-stimulated PR of T-cells from active RAU patients. These results suggest that THL can modulate the antigen-stimulated PR of PBMC and T-cells from RAU patients. Therefore, it may be a potential immunoceutical agent for treatment of RAU.

Cell Culture Techniques↗

PubMed2005

Antiinflammatory and immunomodulating properties of fungal metabolites.

We discuss current information on the ability of extracts and isolated metabolites from mushrooms to modulate immune responses. This can result in a more enhanced innate and acquired disease resistance. The major immunomodulating effects of these active substances derived from mushrooms include mitogenicity and activation of immune effector cells, such as lymphocytes, macrophages, and natural killer cells, resulting in the production of cytokines, including interleukins (ILs), tumor necrosis factor alpha (TNF)-alpha, and interferon gamma (INF)-gamma. In particular, the ability of selective mushroom extracts to modulate the differentiation capacity of CD4(+) T cells to mature into T(H)1 and/or T(H)2 subsets will be discussed. As a consequence these extracts will have profound effects in particular diseases, like chronic autoimmune T(H)1-mediated or allergic T(H)2-mediated diseases. Immunosuppressive effects by mushroom components have also been observed. The therapeutic effects of mushrooms, such as anticancer activity, suppression of autoimmune diseases, and allergy have been associated with their immunomodulating effects. However, further studies are needed to determine the molecular mechanisms of the immunomodulating effects of mushrooms metabolites both individually and in complex mixtures, for example, extracts.

Agaricales↗