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 649 records · Page 36Linked to original sources

PubMed2005

Involvement of TLR6/1 in rLcrV-mediated immunomodulation of murine peritoneal macrophages in vitro.

LcrV of Yersinia pestis is an enigmatic antigenic protein having multiple functions such as effector, translocator and regulator in Type III secretion system. In present study, it is reported that rLcrV causes subversion of macrophage-mediated immune functions. rLcrV treatment down regulated the transcription of IL-12, IRAK-1, MHC-II, phosho-STAT1 and adhesion molecule CD18 in LPS stimulated macrophages. rLcrV induced up regulation of phospho-STAT3 expression, while had no effect on expression of phospho-STAT6. Neutralization and immunoprecipitation experiments suggest the probable involvement of TLR2 and TLR6 heterodimer in rLcrV-mediated immunomodulation of macrophages. Adaptor molecule MyD88, CD11b, and MHC-I expression did not modulate upon treatment with rLcrV.

Animals↗

PubMed2005

Pharmacokinetics, toxicity of nasal cilia and immunomodulating effects in Sprague-Dawley rats following intranasal delivery of thymopentin with or without absorption enhancers.

Thymopentin (TP 5), a synthetic pentapeptide, has been used in clinic as a modulator for immnuodeficiencies through intramuscular administration. The objectives of this study was to investigate the pharmacokinetics using normal rats and toxicity of nasal cilia as well as immunomodulating effects using immunosuppression rats after intranasal delivery of thymopentin with or without an absorption enhancer. The absorption extent of fluorescein isothiocyanate (FITC) labeled TP 5 via nasal delivery at a single dose is significantly improved by incorporating sodium deoxycholate, Brij 35 and chitosan, respectively. FITC-TP 5 can also be absorbed to such an extent ranging from 15 to 28% after intranasal administration of FITC-TP 5 alone, FITC-TP 5 with sodium caprylate, or with bacitracin, respectively. After seven consecutive days multiple dosing, TP 5 formulation with sodium deoxycholate or Brij 35 caused apparently injury to nasal cilia, indicating these two enhancers would not be appropriate for nasal delivery. Results from superoxide dismutase activity, maleic dialdehyde, T-lymphocyte subsets (CD3+, CD4+, CD8+ and CD4+/CD8+ ratio) analyses suggest that all the selected enhancers improve the modulating effects of TP 5 in the immunosuppression rats. On an overall evaluation, intranasal TP 5 alone, TP 5 with chitosan, or TP 5 with bacitracin formulation may be suitable for the future clinical application.

Absorption↗

PubMed2005

FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary lymphoid tissues and thymus by agonistic activity at sphingosine 1-phosphate receptors.

FTY720 is the first of a new immunomodulator class: sphingosine 1-phosphate (S1P) receptor agonist. In 1994, an immunosuppressive natural product, ISP-I (myriocin), was isolated from the culture broth of Isaria sinclairii, a type of vegetative wasp. The chemical modification of ISP-I yielded a new compound, FTY720, which has more potent immunosuppressive activity and less toxicity than ISP-I does. FTY720 has been shown to be highly effective in experimental allotransplantation models and autoimmune disease models. A striking feature of FTY720 is the induction of a marked decrease in peripheral blood T- and B-cells at doses that show immunosuppressive activity in these models. Reportedly, FTY720 is rapidly converted to FTY720-phosphate (FTY720-P) by sphingosine kinase 2 in vivo, and FTY720-P acts as a potent agonist at S1P receptors. Recently, it has been suggested that FTY720-P internalizes S1P1 on lymphocytes and thereby inhibits the migration of lymphocytes toward S1P. Thus, it is likely that the reduction of circulating lymphocytes by FTY720 is due to the inhibition of S1P/S1P1-dependent lymphocyte egress from secondary lymphoid tissues and thymus. Because FTY720 displays a novel mechanism of action that has not been observed with other immunosuppressive agents and shows a synergism with cyclosporin A (CsA) and tacrolimus, it is presumed that FTY720 provides a useful tool for the prevention of transplant rejection and a new therapeutic approach for autoimmune diseases including multiple sclerosis and rheumatoid arthritis.

Animals↗

PubMed2007

Immunomodulating polysaccharides from the lichen Thamnolia vermicularis var. subuliformis.

Three heteroglycans Ths-4, Ths-5 and thamnolan and a beta-glucan, Ths-2, isolated from the lichen Thamnolia vermicularis var. subuliformis were tested for in vitro immunomodulating activities and shown to have various influences on the immune system. All the polysaccharides except Ths-4 caused a stimulation of rat spleen cell proliferation. In contrast, Ths-4 caused cell death early in the culture, probably due to over-stimulation. Moreover, the galactofuranomannans, Ths-4, Ths-5 and the beta-glucan Ths-2, induced rat spleen cells to secrete IL-10 significantly above background levels. In addition, Ths-4 and Ths-5 stimulated significant TNF-alpha secretion by rat peritoneal macrophages. The galactofuranomannans Ths-4 and Ths-5 have similar structures apart from the molecular weight. Thus, it may be concluded that the molecular size might influence the potency but not the pattern of activity for Ths-4 and Ths-5. The galactofuranorhamnan thamnolan had less mitogenic effect than Ths-5 and Ths-2 and neither induced IL-10 secretion by rat spleen cells nor TNF-alpha secretion by peritoneal macrophages to significant levels. This shows that thamnolan with its unusual galactofuranorhamnan structure differs from the other Thamnolia polysaccharides in its immunomodulatory activity.

Animals↗

PubMed2004

Is JAK3 a new drug target for immunomodulation-based therapies?

JAK3, a member of the Janus kinase family, has a crucial role in T-cell development and the homeostasis of the immune system because of its association with the common gamma chain (gammac) of cytokine receptors. Disruption of either JAK3 or gammac expression results in severe combined immunodeficiency disease. Thus, JAK3 has attracted significant attention in recent years as a target for therapeutic intervention in several immune-related diseases. Inhibitors of JAK3 have been developed that might act as either immunosuppressive agents in human organ transplantation or as immunomodulators in autoimmune disorders. We propose that targeting JAK3 offers alternative avenues for the development of new immunomodulatory strategies of therapeutic value. Furthermore, we believe that in addition to the tyrosine kinase domain of JAK3, where inhibitor design efforts are currently focused, non-catalytic regions of JAK3 might represent candidate targets for future drugs.

Animals↗

PubMed2004

Analysis of immunomodulating nitric oxide, iNOS and cytokines mRNA in mouse macrophages induced by microcystin-LR.

Microcystins (MCs) are the toxic molecules produced by common cyanobacterium in freshwater blooms. Their toxicities have brought severe health issues to livestock and human being. Microcystin-LR (MC-LR) is one of the most toxic MCs. This paper presents the profile of the immunomodulation of MC-LR to BALB/c mice peritoneal macrophages. Macrophages were stimulated with 100microg/l lipopolysaccharide (LPS) and MC-LR at dose of 1, 10, 100, 1000nmol/l, respectively, for 24h. Nitric oxide (NO) production in cell culture supernatants was quantified by using Griess reagent method. Total RNA was extracted from incubated macrophages then the mRNA abundance of induced nitric oxide synthase (iNOS), IL-1beta, TNF-alpha, GM-CSF, IFN-gamma was monitored by using reverse-transcriptional polymerase chain reaction (RT-PCR). The results demonstrated that NO production, mRNA levels of iNOS, IL-1beta, TNF-alpha were down regulated by MC-LR dose-dependently and mRNA levels of GM-CSF and IFN-gamma were also decreased but in dose-independent manner. Our results illustrated the involvement of NO production, iNOS and some cytokines in mice immune system in microcystin shock.

Adjuvants, Immunologic↗

PubMed2003

Influence of 1,25-dihydroxyvitamin D3 as an immunomodulator in renal transplant recipients: a retrospective cohort study.

Many studies suggest that 1,25-dihydroxyvitamin D3 (1,25-[OH](2) D3) and its analogues are potent dose-reducing drugs for other immunomodulators, helping to prevent graft rejection. In this study, we retrospectively grouped renal transplant recipients into two cohorts based on 1,25-[OH](2) D3 use to analyze the immunomodulatory effects. Ninety-two subjects were initially enrolled: group A (n = 43) recipients who had osteoporosis and were treated with 1,25-[OH](2) D3, and group B (n = 49) was a control group. We evaluated the effects on the number of acute rejection episodes, the immunosuppressive drug doses, serum calcium levels, and overall graft survival. Although before treatment the number of acute rejection episodes was statistically higher among group A than group B patients, after introduction of 1,25-[OH](2) D3, the difference became nonsignificant. This study showed that osteoporotic renal transplant recipients experienced fewer acute rejection episodes after 1,25-[OH](2) D3 treatment.

Adult↗

PubMed2004

FTY720 immunomodulation: optimism for improved transplant regimens.

FTY720, a sphingosine 1-phosphate receptor (S1P-R) agonist, is the first in a new class of immunomodulators. FTY720 has been shown to be highly effective for preventing graft rejection in preclinical models of cardiac, renal, and hepatic transplantation. To date, phase I single and multiple dosing studies conducted in stable renal transplant patients have revealed a favorable efficacy and tolerability profile. Following these preliminary clinical evaluations, phase II studies have determined optimal dosing for prevention of acute rejection and the efficacy and tolerability of FTY720 in combination with reduced and full-dose cyclosporine (CsA). Data available for these studies demonstrate that FTY720 5 mg combined with reduced-dose CsA provides equivalent freedom from acute rejection to a standard mycophenolate mofetil (MMF)/CsA regimen. Moreover, rejection prophylaxis with a 5-mg dose of FTY720 appears to allow for a 50% reduction in the dose of calcineurin inhibitors while effectively preventing graft rejection. These studies have also shown that FTY720 has no overlapping toxicity with classical immunosuppressive agents; FTY720 can be used safely in combination with CsA and everolimus. Overall, these synergistic effects suggest that FTY720 has the potential to provide a real improvement in the efficacy and tolerability of future immunosuppressive regimens.

Clinical Trials as Topic↗

PubMed2006

Proteliposome-derived Cochleate as an immunomodulator for nasal vaccine.

Proteoliposome (PL) has been recently used as a protective intramuscular (i.m.) anti-meningococcal BC vaccine. It induces a preferential Th 1 type of immune response. Nevertheless, mucosal protection is mainly mediated by IgA antibody response, which is not usually induced by i.m. vaccination route. IgA antibody production needs the stimulation of Th3 subpopulation, which is also related to the induction of small dose tolerance. We hypothesized that PL-derived Cochleate can induce a specific mucosal IgA and systemic IgG antibody responses. We could show that mice immunized with two or three intranasal doses of PL-derived Cochleate developed significantly increased levels of local anti PL IgA and systemic IgG antibody responses. Thus, our results suggest that PL-derived Cochleate can be used as a promising immunomodulator and delivery system for the development of mucosal, particularly nasal vaccines.

Adjuvants, Immunologic↗

PubMed2006

Liposomal preparations of muramyl glycopeptides as immunomodulators and adjuvants.

The need for safe and structurally defined immunomodulators and adjuvants is increasing in connection with the recently observed marked increase in the prevalence of pathological conditions characterized by immunodeficiency. Important groups of such compounds are muramyl glycopeptides, analogs of muramyl dipeptide (MDP), glucosaminyl-muramyl dipeptide (GMDP), and desmuramylpeptides. We have designed and synthesized new types of analogs with changes in both the sugar and the peptide parts of the molecule that show a high immunostimulating and adjuvant activity and suppressed adverse side effects. The introduction of lipophilic residues has also improved their incorporation into liposomes, which represent a suitable drug carrier. The proliposome-liposome method is based on the conversion of the initial proliposome preparation into liposome dispersion by dilution with the aqueous phase. The description of a home-made stirred thermostated cell and its link-up with a liquid delivery system for a rapid and automated preparation of multilamellar liposomes at strictly controlled conditions (sterility, temperature, dilution rate and schedule) is presented. The cell has been designed for laboratory-scale preparation of liposomes (300-1000 mg of phospholipid per run) in a procedure taking less than 90 min. The method can be readily scaled up. Examples of adjuvant and immunostimulatory effect of liposomal preparation in mice model will be presented.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2005

Protection of turkeys against Chlamydophila psittaci challenge by DNA and rMOMP vaccination and evaluation of the immunomodulating effect of 1 alpha,25-dihydroxyvitamin D(3).

Plasmid DNA expressing the major outer membrane protein (MOMP) of an avian Chlamydophila psittaci serovar D strain and recombinant MOMP (rMOMP) with or without the immunomodulating adjuvant 1 alpha,25-dihydroxyvitamin D(3) have been tested for their ability to elicit an immune response and induce protection in turkeys against challenge with the same serovar. Three vaccination strategies were compared: priming and boosting with either pcDNA1::MOMP or rMOMP and priming with pcDNA1::MOMP followed by rMOMP boosting. Turkeys primed with pcDNA1::MOMP showed significant protection against Cp. psittaci challenge, turkeys primed with rMOMP did not. The steroid hormone 1 alpha,25-dihydroxyvitamin D(3) augmented serum and mucosal antibody titres. However, higher antibody titres were not related to better protection and even had a negative effect on especially bacterial excretion.

Adjuvants, Immunologic↗

PubMed2004

Differentially expressed genes in HIV-1-infected macrophages following treatment with the virus-suppressive immunomodulator murabutide.

The synthetic immunomodulator murabutide has been found to suppress human immunodeficiency virus type-1 (HIV-1) replication, in macrophages, through a regulated expression of cellular factors needed at different steps in the virus replication cycle. To identify cellular genes implicated in the murabutide-induced virus inhibition, we have carried out a differential display analysis on HIV-1-infected macrophages that were treated, or not, with murabutide. Sequencing of the differentially regulated cDNA bands and verification of the reproducibility of the murabutide effects, by reverse transcription-polymerase chain reaction or by Northern blotting, revealed an up-regulated expression of 21 genes and a down-regulation of seven others. The murabutide-regulated genes encoded proteins implicated in DNA binding, regulation of transcription, oxidative stress, metal binding, and other physiological functions. Six of the genes corresponded to unassigned/expressed sequence tags with yet unknown function. Among the genes which were up-regulated by murabutide and with established effects on inhibiting virus transcription, was the octamer binding factor 1 (Oct-1). We demonstrate the ability of murabutide to induce enhanced Oct-1 protein expression and DNA-binding activity in macrophages. Furthermore, our findings suggest the potential implication of additional transcription factors and metal-binding proteins in mediating the inhibitory effect of murabutide on virus transcription.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2005

A murine model of dual infection with cytomegalovirus and Pneumocystis carinii: effects of virus-induced immunomodulation on disease progression.

Despite the use of antimicrobial prophylaxis, cytomegalovirus (CMV) and Pneumocystis carinii (PC) pneumonia (PCP) are both leading causes of morbidity and mortality in immunocompromised patients. It has previously been reported that CMV infection modulates host immune responses with a variety of mechanisms which include the suppression of helper T cell functions and antigen presenting cell (APC) functions, both of which are critical for PCP resolution. However, the mechanisms of these interactions and other possible immune regulatory effects are not clearly understood. In this study, we investigated the impact of murine CMV (MCMV) induced immunomodulation on the progression of PCP in a co-infection model. Initial results show that dually infected mice had evidence of more severe PC disease, which include a greater loss of body weight, an excess lung PC burden and delayed clearance of PC from lungs, compared to mice with PC infection alone. At day 7 post-infection, dually infected mice had reduced numbers of MHC-II expressing cells in the lung interstitium and lymph nodes and reduced migration of CD11c+ cells to both the tracheobronchial lymph nodes and alveolar spaces. Dual infected mice showed elevated numbers of specific CD8 responses concomitant with a decrease in activated CD4+ T cells in both the lymph nodes and in alveolar spaces when compared to mice infected with MCMV alone. These data suggest that MCMV infection inhibits the immune responses generated against PC which contribute to the delayed clearance of the organism.

Animals↗

PubMed2005

Phase III double-blind randomized trial of radiation therapy for stage IIIb cervical cancer in combination with low- or high-dose Z-100: treatment with immunomodulator, more is not better.

BACKGROUND: To evaluate the efficacy of low or high-dose immunomodulator, Z-100, in combination with radiotherapy for cervical cancer. METHODS: Between 1995 and 1999, 221 patients with stage IIIb squamous cell carcinoma of the cervix were randomly assigned to treatment with Z-100 either at 0.2 microg or 40 microg in a double-blind manner in combination with radiotherapy. RESULTS: The 5-year survival of patients with high-dose and low-dose Z-100 was 41.5% (95% CI: 31.7-51.3%) and 58.2% (95% CI: 48.7-67.7%), respectively, showing a 30% reduction in the death rate (hazard ratio: 0.670 [95% CI: 0.458-0.980], P = 0.039). Survival of high-dose group was equivalent to the 4-year survival of the radiotherapy plus hydroxyurea arm (49.7%) of GOG120 study, and that of low-dose group was similar to the survival of the cisplatin-based chemoradiation arm. The progression-free survival was also significantly improved in favor of low-dose group (hazard ratio: 0.667 [95% CI: 0.447-0.997], P = 0.048). The survival of low-dose group was similar to the survival of the cisplatin-based chemoradiation arms of the GOG120 study. CONCLUSIONS: Unexpectedly, the survival of patients with advanced cervical cancer treated by lower dose of Z-100 in combination with radiotherapy was significantly better than those treated with higher dose Z-100, which was equivalent to the survival with radiotherapy alone. The hypothesis that lower dose of Z-100 enhances the efficacy of radiation therapy is now being tested by placebo-controlled randomized trial.

Adjuvants, Immunologic↗

PubMedDate not supplied

Bovine haptoglobin as a possible immunomodulator in the sera of transported calves.

Bovine haptoglobin, which has been recognized as an acute phase protein following tissue injury and inflammation, was detected as a 33 k + 20 k Dalton fraction in the sera from calves transported by road for 2 days. The sera also possessed suppressive activity on lymphocyte proliferative response to concanavalin A. A significant correlation (r = 0.57, P < 0.05) was observed between haptoglobin concentrations and lymphocyte suppression in the sera. Furthermore, the haptoglobin fraction obtained from acute phase sera exerted dose-dependent suppression on lymphocyte blastogenesis. These circumstantial data suggest the possible involvement of bovine haptoglobin, at least in part, as an immunomodulator in serum suppression of lymphocyte blastogenesis in transported calves.

Adjuvants, Immunologic↗

PubMed2002

TH1 and TH2 cytokine inhibition by 3,5-bis(trifluoromethyl)pyrazoles, a novel class of immunomodulators.

In order to discover novel immunomodulators for application in treating autoimmune diseases, a stable Jurkat transfectant was constructed in which luciferase reporter gene is driven by a full-length IL-2 promotor. A chemical library was screened to identify compounds that inhibited luciferase expression in Jurkat transfectants stimulated with PMA and ionomycin. A class of compounds (bis-trifluoromethyl pyrazole, BTPs) was identified from this screen. BTPs were shown to inhibit anti-CD3 and anti-CD28 antibody-induced IL-2 secretion, mixed lymphocyte reaction, and Con A-induced T cell proliferation in normal human peripheral blood T cells. In addition, mRNA levels of IL-4, IL-5, IL-9, IL-10, IL-13, IL-15, and IFN-gamma were markedly inhibited by BTPs in peripheral blood mononuclear cells stimulated by Con A as determined by multi-probe RNA protection assay. Furthermore, IL-2, IL-4, IL-5, and IFN-gamma secretion by Hut 78 cells or CD3(+) T cells stimulated with PMA plus ionomycin or anti-CD3 antibody plus PMA were inhibited in a concentration-dependent manner by BTPs. Therefore, BTPs inhibit a wide spectrum of cytokine production including TH1 and TH2 type cytokines. Taken together, these compounds may be useful for treating autoimmune diseases and organ transplant rejection.

Adjuvants, Immunologic↗

PubMed1997

Interest of immunomodulation as a mean to improve the preparation of polyclonal and monoclonal antibody reagents.

Immunomodulation by monoclonal antibodies (mAbs) was investigated in mice in order to improve the preparation of antibody reagents. Three different types of representative immunogens were chosen: a human soluble protein (secretory immunoglobulin A, SIgA), a bacterial polysaccharide from E. coli K1 and an envelope protein from the hepatitis B virus. These Ag are all of importance for diagnosis and exhibit different levels of immunogenicity. Antibody-mediated enhancement was observed against restricted and defined regions of each immunogen i.e.: the Fab epitopes of SIgA, the preS1 domain of the HBV envelope and associated cell wall components of the capsular PS. The epitopes which were enhanced appeared to be different from those recognized by the modulating mAb. Negative modulations were also observed. Moreover, new epitopes seemed to be generated. In both cases the level and direction of the modulation were irrespective of isotypy and affinity of the mAbs. Interestingly the positive modulatory effect was found to be correlated with an in vitro assay based on the binding of immune complex to antigen-presenting cells.

Animals↗

PubMed1984

The effect of the immunomodulator corynebacterium parvum on hemisplenectomized mice.

The immunomodulator Corynebacterium parvum stimulates the reticuloendothelial system and causes splenic hypertrophy. The ability of C parvum to stimulate splenic regeneration in hemisplenectomized mice and decrease susceptibility to intranasal pneumococcal challenge was studied. Mice were divided into two groups, control sham-operated (n = 48) and hemisplenectomized (n = 47) animals. Ten days later, each group was divided into two subgroups, those injected with C parvum (700 mcg IVP) and those injected with an equivalent volume of saline. The animals were challenged with Streptococcus pneumoniae, which was injected into one nostril three weeks postoperatively, and mortality was assessed. Four and one-half weeks postoperatively, splenic tissue was removed, measured, weighed, and submitted for histologic examination. The number of spleen cells per gram of tissue was assessed. Treatment with C parvum resulted in a significant increase in the splenic weight in both hemisplenectomized and control animals compared to similar saline-injected mice (P less than 0.001). The percentage increase in spleen weight of hemisplenectomized mice (106%) was significantly greater than that for control animals (56%; P less than 0.01). There was no significant difference among experimental groups in the number of spleen cells per gram of splenic tissue or in the histologic characteristics, indicating that C parvum stimulated relatively normal splenic growth. Survival following pneumococcal challenge was significantly increased for hemisplenectomized mice by C parvum treatment to a level that did not significantly differ from control mice. This study demonstrates that in mice the deficits related to resistance to infection and spleen size following hemisplenectomy are significantly improved by treatment with C parvum.

Adjuvants, Immunologic↗