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Results for “immunomodulation”

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At least 217 records · Page 12Linked to original sources

PubMed1994

Activation of human T helper 1 and DNAase expression in CD4+ T cells induced by short immunomodulating peptides.

Activation of human T helper 1 cells took place when lymphomononuclear cells from healthy donors were incubated in the presence of short synthetic peptides encompassing sequences present in extracellular matrix proteins. Active peptides conformed to a common structural pattern ("2-6-11 motif") [N.López-Moratalla et al., Biochem. Biophys. Acta (1994) 1221, 153-158] conferring immunomodulating properties. The release of IL-2 and IFN gamma, as well as LAK and NK-dependent cytotoxicity induced by these peptides, could be blocked by anti-HLA-DR antibody. Activated CD4+ cells isolated from the mixed incubated population contained secretion granules with DNAase activity. These results suggest that these immunomodulating peptides presented by HLA-II play a key role in the differentiation of CD4+ T cells towards a Th1 functional phenotype.

Adjuvants, Immunologic↗

PubMed1993

Antigen presentation of mycobacterial peptides to human T cell clones can be immunomodulated by adding an MHC-specific inhibitor.

The immunomodulation of T cell recognition by mycobacterial antigens was investigated using T cell clones activated with peptide-pulsed EBV-B cells. An HLA-DR1-restricted T cell clone from a patient with tuberculosis responded to peptide 65-85 from the 65-kDa protein of Mycobacterium tuberculosis in a dose-dependent manner, while no significant response was induced by antigen-nonpulsed EBV-B cells or EBV-B cells pulsed with an unrelated antigen (streptokinase/streptodornase). The observed binding to HLA-DR1 could be inhibited when the EBV-B cells were cultured in the presence of an excess of an HLA-DR1-restricted T cell epitope (residues 1-20) from the 19-kDa protein of M. tuberculosis. This inhibition was dose-dependent. In other experiments, proliferation of a DR1-restricted T cell clone from a healthy individual which responded to peptide 1-20 was inhibited by an excess of peptide 65-85, confirming that these peptides are able to compete for the same DR1-binding site. Nevertheless, the T cell clone from the healthy individual showed a relatively lower percentage of inhibition compared with the T cell clone from a patient with tuberculosis. Furthermore, the intensity of this inhibition was reversed as the concentration of stimulatory peptide was increased. The experiments described in this paper demonstrate the immunomodulation of mycobacterial antigen presentation by peptide competition at the level of MHC-binding sites. These data may be important for an understanding of the interactions involved in the mycobacterial cell-mediated immune recognition.

Antigen-Presenting Cells↗

PubMed1995

Marijuana, receptors and immunomodulation.

THC, the major psychoactive component of marijuana, has been shown both in humans and experimental animals to have immunomodulatory properties. For example, marijuana smokers may show impaired immunological functions, including deficiency of blood leukocyte blastogenesis to mitogens. Detailed studies with mice have shown that animals given THC can show marked immunomodulation, including suppression of antibody formation, deficient cytokine production, etc. However, recent studies have also shown that lymphoid cells evince enhanced production or release or IL1, but suppression of IL2 and interferon production. Such lymphoid cells treated in vitro with THC also show suppressed blastogenesis to antigens and mitogens, suppressed NK activity, etc. In contrast, it has recently been shown that THC can enhance production or release of pro-inflammatory cytokines. This includes release of these cytokines from macrophages, including augmented release of IL1, TNF alpha, and IL6 activity. Susceptibility of mice to infection with opportunistic organisms such as L. pneumophila has been found and this increased susceptibility can be modulated by THC. A toxic shock-like death to Legionella has been induced by THC treatment given one day before and one day after infection. Receptors to THC have been detected in the brain as well as in peripheral tissues, including lymphoid cells. Thus, immunomodulation induced by THC may be related to receptor effects as well as unrelated to such receptors. It is clear that THC and other cannabinoids are excellent tools for studying the mechanisms of immune modulation, especially altered susceptibility to microbial infection.

Adjuvants, Immunologic↗

PubMed1988

Immunomodulators.

A new era is emerging in the therapy of rheumatic disease involving the use of biologically based immunomodulators. Cytokines, such as the interleukins and interferons, are proteins produced by activated lymphoid cells which can now be synthesised by genetic engineering techniques. These agents have already been used to correct "immune deficiencies" in patients with neoplastic and inflammatory disease e.g. gamma-interferon in rheumatoid arthritis (RA). Monoclonal antibodies (mca) targeted against lymphocyte cell surface receptors or against autoantibodies have been successfully applied in human lymphoid malignancies, organ transplantation and in animal models of arthritis. Potential problems in man include the development of allergic reactions to mouse proteins and of antibody resistance. Although in its infancy, immunomodulation represents an exciting approach to the treatment of rheumatic disease.

Adjuvants, Immunologic↗

PubMed1985

Combined therapeutic effects of an immunomodulator, PSK, and chemotherapy with carboquone on rat bladder carcinoma.

Responses of bladder cancer in ACI rats to combination therapy with an immunomodulator, PSK, and an alkylating agent, carboquone, are reported. PSK is a protein-bound polysaccharide isolated from Basidiomycetes, and carboquone is the alkylating agent 2,5-bis(1-aziridinyl)-3-(2-hydroxy-1-methanoxyethyl)-6-methyl-p- benzoquinone carbonate, molecular weight 3,214. The immunomodulator, PSK, was shown to enhance the effectiveness of the chemotherapeutic agent, carboquone. The therapeutic effect of combination treatment was monitored by measuring growth rates of tumors transplanted SC and by measuring decreases in metastatic spread to lungs in tumor-bearing animals. Effects of PSK on host immunity were monitored by measuring serum levels of immunosuppressive substance.

Adjuvants, Immunologic↗

PubMed1997

Immunomodulating activity of allopurinol in experimental lens-induced uveitis.

PURPOSE: The aim of this study was to evaluate the immunomodulating activity of allopurinol using a model of lens-induced uveitis (LIU) and to compare these effects to those of steroids. METHODS: We tested the sera of both LIU and control rats against western blots (WB) of SDS-PAGE separations of protein fractions from normal and LIU rat lenses. These blots were scanned using digital image analysis. A newly developed technique was used to compare the complex autoantibody (AAB) repertoires. Five groups of LIU rats were investigated: no treatment; single doses of methylprednisolone (MPR; 7.5 mg/kg body wt.i.v.); allopurinol (AL; 50 mg/kg body wt. i.v.); a combination of both drugs (AL and MPR); repeated application of AL (ALFR; 50 mg/kg body wt.i.v. every 2 weeks during the immunization period and a daily dose of approx. 25 mg/kg body wt. orally). RESULTS: Immunization induced complex antibody repertoires against lens proteins. Antibody repertoires of LIU rats were identical, regardless of whether the proteins were obtained from control, uveitis eyes, or corresponding healthy eyes of the same individual. AL showed a dose-dependent immunological effect in LIU treatment. Given as a single dose, AL revealed no significant change in the AAB repertoire; however, ALFR showed very clear modification of the AAB repertoires compared to both controls and rats receiving steroids. CONCLUSIONS: These results suggest dose-dependent effects of allopurinol in LIU treatment. Repeated application during the immunization period induced a strong immunomodulating effect of AL that was not observed after single doses.

Adjuvants, Immunologic↗

PubMed1991

In vitro immunomodulating effect of protein-bound polysaccharide, PSK on peripheral blood, regional nodes, and spleen lymphocytes in patients with gastric cancer.

PSK, a protein-bound polysaccharide, has been widely used for cancer immunotherapy in Japan. However, the mechanism of its immunomodulatory effect has not been fully clarified. In the present study the in vitro effect of PSK on the lymphocytes of patients with gastric cancer was studied. Culturing lymphocytes with PSK at 5-100 micrograms/ml increased the level of DNA synthesis, and augmented the cytotoxicities against K562 and KATO-3. Flow-cytometric analysis also showed an increase in the proportion of interleukin-2 (IL-2)-receptor-positive cells after the lymphocytes were cultured with PSK. However the cytotoxicity of cells cultured with PSK was not augmented by the addition of recombinant interferon gamma (rIFN gamma) and rIL-2. Further experiments using fractionated PSK showed that its biological action is present mainly in fractions having molecular masses greater than 10(5) Da. However, these immunomodulations were not seen in all patients. These results suggest that the susceptibility of lymphocytes to PSK may be different in each patients, and that the immunomodulation by PSK may be mediated by mechanisms independent of IFN and IL-2.

Adjuvants, Immunologic↗

PubMed1982

Effect of immunomodulating agents on leucocyte chemotaxis and cyclic nucleotides.

We have studied the effect of immunomodulating agents on polymorphonuclear leucocyte chemotaxis and their relation to the modification of cyclic nucleotide levels. The tested drugs (levamisole, tuftsin, azimexon, muramyl dipeptide, isoprinosine) inhibited the chemotaxis of 'normal' cells but restored the impaired chemotactic responsiveness of inflammatory cells. None of these drugs had any significant effect on cyclic nucleotide levels in 'normal' cells. All the drugs, except isoprinosine, produced an increase in the cGMP levels in inflammatory cells. These results suggest that immunomodulators are able to modify PMN chemotaxis. This effect cannot, however, be related to modification of the cyclic nucleotide levels.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1989

FCE20696, a new synthetic immunomodulator: immunopharmacological profile.

A preliminary characterization of the immunopharmacological profile of the new immunomodulating agent FCE20696 (6H,6[2-(dimethylamino)-ethoxycarbonyl]-dibenzo[b,d]pyran-HCl) was performed in mice. Single i.p. doses of this chemical, concomitantly given with the antigen, increased the antibody response and decreased the delayed hypersensitivity reaction to a suboptimal dose of SRBC, the active doses ranging from 6.25 to 50 mg/kg. No activity was observed using a full antigen dose. Macrophage cytotoxic activity was enhanced 2-4 days after a single i.p. treatment with 50 and 10 mg/kg. Spleen cell proliferation to T and B mitogens was inhibited by a single dose of 30 mg/kg given i.p. 6 days before the test, or by 10 mg/kg x 3 days ending one day before the test. Finally, generation of suppressor cells was enhanced by the compound, given p.o. biweekly for at least 7 weeks, at doses ranging from 0.1 to 10 mg/kg. Collectively taken, these data suggest that FCE20696 has a broad range of immunomodulating activities and that macrophages and suppressor cells are presumed to be the main targets of its pharmacological activity.

Adjuvants, Immunologic↗

PubMed1989

The effect of immunomodulating drugs on adjuvant-induced arthritis in Lewis rats.

The purpose of this study was to investigate the effects of cyclosporine A (CSA) and methotrexate (MTX) as potential immunomodulators in a nonestablished adjuvant arthritis (AA) model. Non-injected hind paw volumes were reduced when AA rats were treated for 18 days with CSA (100% at 10 mg/kg) or MTX (100% at 0.1 mg/kg). Body weights of drug treated AA rats were increased above untreated AA rats and were similar to non-arthritic controls. AA rats show elevated T helper (W3/25+)/T suppressor (OX 8+) cell ratios (2.0 vs. 3.1, p less than 0.01). The immunomodulators tested all returned these elevated ratios to control non-arthritic levels. Similarly, these drugs returned the reduced mitogen responses and elevated blood granulocyte numbers toward normal non-arthritic control values.

Animals↗

PubMed1994

Immunomodulator therapy in inflammatory bowel disease.

The introduction of immunomodulator therapy in the treatment of patients with inflammatory bowel disease (IBD) has provided an important tool in modifying the mucosal immune system thought to be important in the pathogenesis of IBD. Currently available immunomodulating agents include azathioprine, 6-mercaptopurine, cyclosporin, and methotrexate. Recent clinical trials have demonstrated that these agents have an important therapeutic role in the treatment of patients who are either refractory or intolerant to traditional medical therapy. They are useful in the induction and maintenance of remission for both ulcerative colitis and Crohn's disease. However, these agents have significant toxicities and limited efficacy. In addition, potential risks of malignancy and infection limit their indiscriminate use. Thus, with the better understanding of the molecular basis of mucosal immunity, innovative immune-modifying therapies, such as antagonists of cytokines and inhibitors of T-cell activation, are being developed. It is likely that these exciting developments will soon result in specific immune modulating therapy with improved efficacy and reduced toxicity in the treatment of patients with IBD.

Antibodies, Monoclonal↗

PubMed2000

Immunomodulating activity of a polysaccharide isolated from Mori Cortex Radicis.

The immunomodulating activity of a polysaccharide isolated from Morus alba (PMA) root bark was examined in murine splenic lymphocytes. PMA enhanced proliferation of splenic lymphocytes in a synergistic manner in the presence of mitogens. However, PMA suppressed primary IgM antibody production from B cells, which was activated with lipopolysaccharide, a polyclonal activator, or immunized with a T-cell dependent antigen sheep red blood cells. Our observations showed that the immunomodulating activity of PMA increased lymphocyte proliferation and that PMA decreased antibody production from B cells, which was distinct from those of other plant-originated polysaccharides.

Adjuvants, Immunologic↗

PubMed2002

[Immunomodulation in sepsis].

INTRODUCTION: The systemic inflammatory response syndrome is induced by a strong inflammatory reaction which is called sepsis when it is caused by an infection. However, anti-inflammatory therapeutic strategies in septic patients were not successful, indicating a more complex system. It is now clear that systemic hyper-inflammation induces systemic anti- or hypo-inflammation which can lead to total paralysis of the immune system ("immunoparalysis"). METHODS: Several studies were performed to evaluate parameters for describing the patient's immunocompetence. Based on these parameters, pilot trials were initiated to test immunomodulating therapies depending on the patient's immunocompetence. RESULTS: The measurement of monocytic HLA-DR expression, as well as the measurement of ex vivo LPS-induced TNF-a secretion, are suitable to describe the patient's immunocompetence. In addition to classical inflammation markers, the characterization of the inflammatory and infection status is completed by measurement of the plasma cytokines, LBP and PCT. IFN-g or GM-CSF application as well as the removal of inhibitory plasma mediators by hemofiltration/plasmapheresis can reconstitute the immune function in patients with "immunoparalysis". CONCLUSIONS: Immunomodulating therapeutic strategies in septic patients have to orientate on the patient's immunocompetence and inflammatory as well as infectious status: a patient in a hyper-inflammatory phase may need anti-inflammatory therapy whereas a patient in "immunoparalysis" needs immunoreconstitution/immunostimulating therapy.

Adjuvants, Immunologic↗

PubMed1996

Induction of gene expression for nitric oxide synthase by immunomodulating drugs in the RAW264.7 murine macrophage cell line.

We have elucidated the direct effects of PSK (a protein-bound polysaccharide) and OK-432 (a streptococcal preparation), both immunomodulating drugs, on the gene expression for an inducible nitric oxide synthase and on the production of nitric oxide (NO) in the RAW264.7 murine macrophage cell line. As determined by northern blot analysis, both immunomodulating drugs were potent inducers of gene expression for inducible NO synthase when cells were costimulated with interferon-gamma (IFN gamma). Expression of mRNA for the enzyme occurred in a dose-dependent manner after 3 h, when 10-50 micrograms/ml PSK or 0.001-1 KE/ml OK-432 was used. Furthermore, NO was also produced in response to these drugs, as detected by the Griess reagent reaction. The enhancement of NO synthesis was thought to be mediated, in part, through tumor necrosis factor alpha (TNF alpha) induction by these agents, since a neutralizing antibody to TNF alpha significantly suppressed NO production in RAW264.7 cells stimulated with PSK or OK432 in combination with IFN gamma. We speculate that NO production may play a role in tumoricidal and microbicidal activities of PSK or OK-432 in vivo.

Adjuvants, Immunologic↗

PubMed2003

Immunomodulation of tissue-engineered transplants: in vivo bone generation from methylprednisolone-stimulated chondrocytes.

Subcutaneously implanted, in vitro engineered tissue is generally affected by the immune system of the host even in autogenous transplantation. The aim of this study was to investigate immunomodulation of subcutaneously implanted tissue-engineered cartilage transplants by intramuscular methylprednisolone application. Transplants consisted of auricular rabbit chondrocytes, polylactide-polyglycolide co-polymer fleeces and species-specific fibrin or agarose. The transplants were subcutaneously implanted in the ridge. Thereafter, animals were separated into two groups, one with and one without methylprednisolone treatment. The specimens were histologically investigated after 6 and 12 weeks. Fleece fiber degradation was complete after 12 weeks, and all transplants showed areas of calcification. The corticosteroid-treated group presented pronounced trabecular bone generation without fibrous tissue infiltration. The untreated group showed sporadic islets of calcification without coherent bone formation, and adjacent fibrous tissue had infiltrated the transplants. Native controls and corticoid-treated transplants did not exhibit bone generation or signs of fibrous tissue infiltration. This study found that immunomodulation by intramuscular methylprednisolone application protects tissue-engineered autogenous chondrocyte transplants from fibrous tissue infiltration and induces trabecular bone formation.

Animals↗

PubMed1999

Immunomodulative effect of muramyldipeptide in mice with larval toxocarosis.

The phagocytic ability of polymorphonuclear leukocytes, the metabolic activity of peritoneal macrophages, the proliferative response of T- and B-cells, and the production of specific anti-Toxocara antibodies were studied in paratenic hosts with experimental larval toxocarosis after treatment with the immunomodulator muramyldipeptide for 119 days. Peroral infection of mice with 2,500 Toxocara canis eggs partially reduced the numbers of cells and inhibited the activity of all cellular immune-response parameters studied. During most of the experiment the greatest suppression was recorded for the peritoneal-macrophage metabolic activity. Parenteral administration of muramyldipeptide to mice at two doses prior to and after infection restored and significantly stimulated the parasite-inhibited phagocytic ability of blood polymorphonuclear leukocytes, metabolic activity of macrophages, and T-lymphocyte proliferative response. It also elevated the production of specific circulating anti-Toxocara antibodies. The immunomodulator significantly reduced the count of migrating T. canis larvae in the host organism (30.6%) and decreased by half the percentage of larvae in the brain.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2000

Genetic analysis of immunomodulating factors in sporadic Parkinson's disease.

Immunomodulating factors have been shown to play a role in the pathogenesis of Parkinson's disease (PD) by biochemical methods. In order to investigate functionally important genes of the tumor necrosis factor alpha (TNFalpha) pathway we studied the frequency of DNA polymorphisms in the interleukin 6 (IL6), the TNFalpha, and the TNFalpha receptor 1 (TNFR1) genes in 264 sporadic German PD patients and in 183 age and sex matched German healthy controls. Analyzing the TNFalpha-308 polymorphism we found heterozygous individuals carrying alleles 1 and 2 more frequently in patients with a relative risk of 1.56 (p = 0.046, p(c) = 0.13, chi2 = 3.98). In contrast, the frequency of the B/2 haplotype described by the TNFR1-609 and TNFRI+36 polymorphisms was significantly decreased in our PD patients group (p = 0.0097, p(c) = 0.048, chi2 = 6.69) with a relative risk reduced to 0.52. Our results suggest an involvement of immunomodulating factors in the pathogenesis of sporadic PD as revealed by a molecular genetic approach.

Adjuvants, Immunologic↗

PubMed2003

Optimizing immunomodulator therapy for inflammatory bowel disease.

6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) remain the mainstay of immunomodulator therapy for the maintenance of steroid-free remission in patients with inflammatory bowel disease (IBD). Traditional dosing strategies for initiation of thiopurines are often based on weight or empirically chosen. Dosing based on an understanding of an inherited difference in drug disposition and metabolism may provide a safer alternative. The thiopurine methyltransferase (TPMT) enzyme plays a pivotal role in the metabolism of 6-MP and AZA and is critical to the determination of thiopurine toxicity. The therapeutic benefits of thiopurines correlate best with concentration of the active 6-thioguanine (6-TGN) metabolites. Reports suggest that therapeutic response can be maximized when patients achieve therapeutic 6-TGN levels. Pharmacogenetic dosing based on TPMT and pharmacokinetic dosing based on 6-TGN levels may offer a safety and efficacy advantage over traditional dosing strategies and provide a novel mechanism for optimizing immunomodulator therapy in IBD.

Adjuvants, Immunologic↗