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Results for “immunomodulation”

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PubMed1996

Synergistic effects between recombinant interleukin-2 and the synthetic immunomodulator murabutide: selective enhancement of cytokine release and potentiation of antitumor activity.

The use of interleukin-2 (IL-2) in the treatment of cancer has shown limited efficacy and dose-limiting toxicity. Combination therapy with other cytokines and/or chemotherapeutic agents has been attempted to enhance the antitumor activity and to reduce the effective therapeutic dose of IL-2. We recently showed, in vitro and in vivo, a synergistic activity between the synthetic immunomodulator murabutide, which is in clinical stage of development, and another therapeutic cytokine, interferon-alpha (IFN-alpha). The present study was performed to assess a possible potentiation of the biologic activities of IL-2 by its association with murabutide. Human PBMC stimulated in vitro with IL-2 and murabutide showed synergistic levels of induced mRNA accumulation and protein secretion for IFN-gamma, IL-12, and colony-stimulating factors (CSFs). No such effects were obtained on the induction of most inflammatory cytokines, including IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha). Furthermore, the combined administration of murabutide with IL-2 into Meth-A sarcoma-bearing mice resulted in a very significant tumor inhibition as well as in complete tumor regression in nearly 70% of the treated mice. Under the same conditions, treatment with either compound separately had little or no antitumor effect. These preclinical findings will be pursued by the evaluation of the clinical tolerance and biologic activity of the murabutide/IL-2 combination therapy in cancer patients.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2005

Immunomodulating activity of arabinogalactan and fucoidan in vitro.

Many polysaccharides obtained from natural sources are considered to be biological response modifiers and have been shown to enhance various immune responses. Here, we investigated the immunomodulating effects of arabinogalactan (AG) and fucoidan (FU) in vitro. Mouse spleen lymphocytes became cytotoxic to tumor cells after culture with AG and FU at concentrations of 10-100 microg/mL. Also, AG and FU were mitogenic in spleen lymphocytes and peripheral macrophages. Macrophages treated with AG and FU (10-100 microg/mL) exhibited induced tumoricidal activity and increased phagocytosis, lysosomal enzyme activity, and production of nitrite, H2O2, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6. However, AG and FU had little effect on the level of IL-1beta. Thus, the tumoricidal effect of AG- and FU-activated macrophages appeared to be mainly mediated by production of free radicals (NO and H2O2) and cytokines (TNF-alpha and IL-6). These data suggest that AG and FU are activators of lymphocytes and macrophages. This property may contribute to their effectiveness in the immunoprevention of cancer.

Animals↗

PubMed1995

Immunomodulating agents for the management of heart failure with myocarditis and cardiomyopathy--lessons from animal experiments.

We have developed murine models of viral myocarditis induced by the encephalomyocarditis (EMC) virus in which there is a high incidence of severe myocarditis, congestive heart failure and dilated cardiomyopathy. From these models, we have learned of their natural history and pathogenesis and assessed new diagnostic methods and therapeutic and preventive interventions. Our recent studies showed that increased circulating cytokines have been detected in patients with acute myocarditis and cardiomyopathy and suggest that cytokines may play some role in the pathogenesis of myocardial injury in these diseases. In our animal model of EMC virus myocarditis, plasma tumour necrosis factor-(TNF)-alpha was elevated in the acute stage and exogenously administered anti-TNF-alpha antibody improved survival and reduced the myocardial lesion, suggesting the importance of TNF-alpha in the pathogenesis. A recently developed positive inotropic agent, vesnarinone, was effective in the treatment of EMC virus myocarditis by its immunomodulating effects such as inhibition of production of TNF-alpha The plasma angiotensin II level was increased in EMC virus myocarditis, and a new angiotensin II type I antagonist, TCV-116, prevented development of myocarditis.

Adjuvants, Immunologic↗

PubMed1977

Immunomodulation of host resistance to experimental viral infections in mice: effects of Corynebacterium acnes, Corynebacterium parvum, and Bacille calmette-guérin.

Resistance to a representative group of experimental virual infections in mice was significantly enhanced by nonspecific modulation of host defense mechanisms. Corynebacterium acnes, Corynebacterium parvum, and bacille Calmette-Guérin were effective in enhancing host resistance. Animals treated seven to 10 days before inoculation of virus were protected against a lethal infection with Herpesvirus hominis type 2, encephalomyocarditis virus, murine cytomegalovirus, or Semliki Forest virus. The protection of experimental animals against encephalomyocarditis virus infection intitiated by either the intraperitoneal or the respiratory route indicated that C. acnes exerted a systemic, rather than local, effect. A maturation process was required for host defense mechanisms stimulated by C. acnes, as indicated by the failure to enhance resistance in suckling animals. Involvement of cells of the lymphoreticular system was demonstrated by transfer of enhanced resistance against H. hominis type 2 to recipient animals with peritoneal exudate cells harvested from mice pretreated with C. acnes. Finally, these same cells inhibited the progression of herpetic infection in tissue culture. The data suggest that immunomodulation, possibly through activation of macrophages, may offer a method for enhancement of host resistance to viral infections.

Animals↗

PubMed1996

Linomide, an immunomodulator that inhibits Th1 cytokine gene expression.

Linomide (LS-2616, quinoline-3-carboxamide) has strong immunomodulating effects in animal models, inhibiting toxic shock, progressive autoimmune disease and cancer. In humans, linomide strongly reduced the appearance of new lesions in multiple sclerosis yet enhanced immune responses after bone marrow transplantation. In contrast to these clear effects in vivo, attempts to show an effect of linomide in vitro have not been successful and its mode of action remains to be elucidated. Here we show that at concentrations effective in vivo, linomide is active on human peripheral blood mononuclear cells (PBMC), severely inhibiting the induction by Staphylococcus aureus enterotoxin B of mRNA of three cytokine genes expressed in Th1 cells, those for IFN-gamma, IL-2, and tumor necrosis factor-beta. Yet, cell viability was not affected by linomide. The extent of inhibition is dose-dependent on linomide. Linomide also blocked induction of IL-2 and IFN-gamma mRNA by phytohemagglutinin. The inhibitory effect is expressed immediately but can be enhanced significantly by a prolonged exposure of PBMC to linomide, reaching 10-fold. These results support the concept that linomide antagonizes the activation of Th1 cells during a cellular immune response.

Adjuvants, Immunologic↗

PubMed2006

Randomized phase II study of immunomodulator Z-100 in patients with stage IIIB cervical cancer with radiation therapy.

OBJECTIVE: To find the optimal dose of immunomodulator Z-100 in patients with stage IIIB squamous cell carcinoma of the cervix in combination with radiation therapy. METHODS: The patients were randomly assigned to the dosage levels of 2, 20 or 40 mug of Z-100. Z-100 was subcutaneously injected twice a week during radiotherapy and once in two weeks during the maintenance period. The response rate after radiotherapy was evaluated, and the optimal clinical dosage was then determined. Safety of Z-100 was evaluated during the radiation therapy and maintenance therapy. Survival was also evaluated. RESULTS: A total of 116 patients were entered. The adverse reactions were not dose-dependent and no serious toxicities were observed. The response rates were 72.2% (26/36) in the 2 microg group, 84.6% (33/39) in the 20 microg group and 94.3% (33/35) in the 40 microg group (P = 0.006). However, the survival was not significantly different. CONCLUSIONS: The optimal dose of Z-100 was determined to be 40 mug in combination with radiation therapy for stage IIIB cervical cancer. However, impact of Z-100 on survival must be determined by the placebo controlled randomized trial, because survival benefit was not observed in this small population study.

Adolescent↗

PubMed1992

LP-BM5, a murine model of acquired immunodeficiency syndrome: role of cocaine, morphine, alcohol and carotenoids in nutritional immunomodulation.

Potential immunomodulation by nutritional excesses and deficiencies can act as cofactors in human immunodeficient virus infection. The role of nutrition in the development and expression of acquired immunodeficiency syndrome (AIDS) is suggested and evaluated. LP-BM5 murine retroviral infection causes immune changes yielding an acquired immune deficiency syndrome with functional similarities to human AIDS. The value of the murine AIDS model to evaluate, rapidly, immune changes caused by potential cofactors, including nutritional changes, is illustrated.

Animals↗

PubMed1977

Effect of immunomodulators on effector cells involved in antibody-dependent cellular cytotoxicity: Brief communication.

The effect of four immunomodulators (BCG, Corynebacterium parvum, pyran copolymer, and levamisole) on the cellular arm of antibody-dependent cellular cytotoxicity (ADCC) was investigated in mice with 51Cr-labeled chicken erythrocytes employed as targets. All these drugs, except levamisole, stimulated the effector cells of ADCC in the spleen, but the kinetics of their effect differed. Stimulation of the effector cells of ADCC peaked on day 15 after injection of BCG and C. parvum and on day 7 after injection of pyran, which was less efficient in this respect than the two bacterial immunostimulants. The increase in ADCC activity caused by BCG and C. parvum was eliminated by treatment with carbonyl iron of the splenocyte suspensions.

Animals↗

PubMed1988

Immunomodulation of natural killer cell activity by flavone acetic acid: occurrence via induction of interferon alpha/beta.

The investigational drug flavone acetic acid (FAA) systemically augments natural killer (NK) cell activity in normal and tumor-bearing mice and in human cancer patients. The results from the present investigation demonstrate that in vivo administration of FAA induces in a dose-dependent manner high levels of serum interferon (IFN) within 4 hours in BALB/c, C57BL/6, and BALB/c nude mice. Antibody neutralization studies indicated that FAA induced IFN of the alpha/beta type, while molecular hybridization studies demonstrated that FAA rapidly stimulated the production of IFN alpha mRNA in splenic leukocytes. In vivo administration of anti-IFN alpha/beta antibodies to FAA-treated mice inhibited the FAA-induced augmentation of splenic NK cell activity at 4 hours. These results suggest that FAA mediates its anti-tumor effects indirectly by immunomodulation as well as directly by antiproliferative or cytotoxic activity.

Adjuvants, Immunologic↗

PubMed1999

A comparison of the direct and reporter antigen popliteal lymph node assay for the detection of immunomodulation by low molecular weight compounds.

The direct popliteal lymph node assay (PLNA) is a predictive test used to detect the immune-stimulating potential of pharmaceuticals and other low molecular weight compounds (LMWCs) with known autoimmunogenic or sensitizing properties. Two limitations in the PLNA are the existence of false negatives and the inability of the assay to provide mechanistic information. Recently the direct PLNA was modified by incorporating reporter antigens (RA), either TNP-Ficoll or TNP-OVA. In the RA-PLNA, immune stimulation is detected by measuring IgM or IgG TNP-specific antibody-forming cells (AFC) using an enzyme-linked immunospot (ELISPOT) assay. The RA-PLNA, when using potent, known autoimmunogenic compounds, may provide greater sensitivity compared to the direct PLNA and might distinguish LMWCs that have intrinsic adjuvant activity from those that create neo-antigens, using TNP-OVA and TNP-Ficoll, respectively. The purpose of this study was to rigorously compare the two assays. Our first objective was to investigate the interlaboratory reproducibility of the RA-PLNA using four autoimmunogenic LMWC models, plus one negative control LMWC. Subsequently, we tested seven LMWCs with known sensitizing properties and compared the results from the direct and modified assay. The test group included LMWCs thought to be mechanistically distinct and similar to compounds typically encountered in preclinical safety assessment. All control and treatment AFC plaques were collected (76 total), pooled, coded to conceal their source, and counted. The interlaboratory reproducibility of the RA-PLNA was demonstrated with the model autoimmunogenic compounds HgCl2, diphenylhydantoin, D-penicillamine, and the negative control compound phenobarbital, by detecting TNP-specific IgM and polyclonal IgG production to both reporter antigens. Additionally, the sensitizing effects of streptozotocin were identified using an IgG2a ELISPOT with both TNP-OVA and TNP-Ficoll. With the extended test group, the sensitizing effects of aniline, a false negative LMWC in the direct PLNA, was not detected in this study when using the direct PLNA. However, there was an increase of IgG1 AFCs using TNP-OVA, when compared to control (508 +/- 113 vs. 12 +/- 4 respectively). Glafenine, diclofenac, and ibuprofen, all associated with drug-induced anaphylaxis in humans, produced significant increases in IgG1 production to TNP-OVA. Of these three LMWCs, only diclofenac, which has been documented to induce neo-antigen formation, was detected with TNP-Ficoll. Hydralazine immunomodulation could be detected only with the direct PLNA although significant increases in IgM were identified with the co-injection of either reporter antigen. Isoniazid and methyldopa consistently produced negative responses in both assays. In summary, this study has demonstrated acceptable interlaboratory reproducibility of the RA-PLNA, using model autoimmunogenic LMWCs. Additionally, it demonstrated that an advantage of the RA-PLNA was that it identified all anaphylactic-associated LMWCs tested, detected the false negative compound aniline, and revealed what is thought to be the mechanism(s) associated with diclofenac-induced immunostimulation.

Animals↗

PubMed2003

Hair growth induction by the Tellurium immunomodulator AS101: association with delayed terminal differentiation of follicular keratinocytes and ras-dependent up-regulation of KGF expression.

The synthetic immunomodulator AS101[ammonium trichloro(dioxoethylene-o,o')tellurate] was previously found to protect cancer patients from chemotherapy-induced bone marrow toxicity and alopecia. Here we show that AS101 induces hair growth in nude and normal mice. AS101 possesses the dual ability to both induce anagen and retard spontaneous catagen in the C57BL/6 mouse model. Anagen induced by AS101 is mediated by keratinocyte growth factor (KGF), as it is abrogated both in nude mice co-treated with AS101 plus neutralizing anti KGF antibodies and in AS101-treated transgenic mice expressing a dominant-negative KGF receptor transgene in basal keratinocytes. AS101 up-regulates KGF expression by activating the ras signaling pathway in cultured fibroblasts. AS101-induced delayed catagen is associated with inhibition of terminal differentiation marker expression both in nude and C57BL/6 mice epidermal follicular keratinocytes and in cultures of primary mouse follicular keratinocytes induced to differentiate. This activity is associated with relatively sustained elevation of p21waf. Delayed expression of terminal differentiation markers was not induced by AS101 in follicular keratinocytes from p21waf knockout mice. Because similar results were obtained with cultures of primary human keratinocytes and fibroblasts, preliminary case report studies revealed substantial hair growth when AS101 was topically applied on three adolescents who had remained alopeciac 1-2 years after chemotherapy. The results emphasize the unique mode of action of AS101 and highlight its potential clinical use for treating certain types of alopecia.

Adjuvants, Immunologic↗

PubMed1991

A protein-bound polysaccharide immunomodulator, PSK, does not suppress the conversion from 1-(2-tetrahydrofuryl)-5-fluorouracil to 5-fluorouracil in patients with gastric cancer.

Effects of the immunomodulator PSK on the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) to 5-fluorouracil (5-FU) were examined in 10 patients with advanced gastric cancer and who had undergone curative resection. PSK is a protein-bound preparation, extracted from Coriolus versicolor and belongs to Basidiomycetes. The 5-FU concentration in the plasma was 0.024 micrograms/ml at 15 min after the intravenous injection of 400 mg of tegafur and the area under the curve of 5-FU was 0.58 micrograms.h/ml. Following administration of PSK, 3 g/day for 8-14 months, there was no change in the plasma level of 5-FU, in any patient. As the clinical dose of PSK had no apparent influence on the metabolism of tegafur to 5-FU, the combination of PSK and tegafur can be prescribed to treat patients with advanced gastric cancer.

Antibiotics, Antineoplastic↗

PubMed1999

Orbital fibroblast interleukin-6 gene expression and immunomodulation.

PURPOSE: Orbital inflammation is common, but the mechanisms underlying leukocytic infiltration of orbital tissue are poorly understood. We studied human orbital fibroblast (OF) interleukin-6 (IL-6) gene expression in response to proinflammatory stimuli and the effects of dexamethasone (DEX) and cyclosporin A (CSA) on cytokine-stimulated OF IL-6 gene expression. METHODS: Cultured OFs were left unstimulated or incubated with varying concentrations of lipopolysaccharide (LPS), or recombinant (r) interleukin-1-beta (rIL-1beta), tumor necrosis factor-alpha (rTNF-alpha), or interferon-gamma (rIFN-gamma) for 2, 4, 8, or 24 hours. OFs were also incubated with rIL-1beta (0.2, 2.0, 20 ng/ml) alone or in the presence of DEX (10(-8), 10(-7), 10(-6) mol/l) or CSA (3, 30, 300 ng/ml) for 8 hours to determine the effects of these immunomodulating drugs on IL-6 expression. Northern blot analyses were performed to determine OF IL-6 mRNA expression in response to varying concentrations of these agents. Experiments were repeated four times on different cell lines. RESULTS: OFs lacked constitutive IL-6 gene expression. Substantial time- and dose-dependent increases in steady-state IL-6 mRNA expression occurred by 4 hours of LPS or cytokine stimulation (rIL-1beta>rTNF-alpha(>LPS>rIFN-gamma), peaked at 8 hours, and were maintained at 24 hours. DEX caused dose-dependent inhibition of IL-1-induced IL-6 mRNA expression, while CSA potentiated IL-1-induced OF IL-6 mRNA expression. CONCLUSIONS: OFs express IL-6 mRNA in response to proinflammatory stimuli. DEX is a potent inhibitor of OF IL-6 mRNA while CSA increases IL-1-induced OF IL-6 gene expression. These observations may in part explain the lack of CSA effectiveness in human orbital diseases that respond to corticosteroids.

Blotting, Northern↗

PubMedDate not supplied

Intensified regression of colon cancer liver metastases in mice treated with irinotecan and the immunomodulator JBT 3002.

The authors recently reported that tumoricidal activation of macrophages by a new synthetic bacterial lipopeptide, JBT 3002, can augment chemotherapy-mediated tumor-cell killing. The aim of this study was to identify the mechanism responsible for the destruction of metastatic cells. Three daily oral doses of JBT 3002 before once-weekly intraperitoneal injections of 100 mg/kg irinotecan for 3 weeks significantly increased the eradication of established CT-26 murine colon cancer liver metastases compared with treatment with irinotecan alone. Immunohistochemical analyses revealed that the hepatic metastases in mice given combination therapy contained infiltrating CD8+ lymphocytes and a dense infiltrate of macrophages expressing both inducible nitric oxide synthase (iNOS) and interleukin-15. In vitro treatment of peritoneal macrophages with JBT 3002 plus interferon-gamma induced the expression of iNOS and the production of nitric oxide. In the presence of a low (subtoxic) dose of irinotecan, these activated macrophages produced significant lysis of CT-26 cells. The high level of cytotoxicity was inhibited by the specific inducible nitric oxide synthase inhibitor, NG-methyl-L-arginine. In contrast, irinotecan-mediated lysis of normal intestinal epithelial IEC-6 cells was not increased by activated macrophages. Scanning electron microscopy revealed that activated macrophages bound to CT-26 tumor cells but not to normal IEC-6 cells, confirming that nitric oxide-mediated cytotoxicity is specific for tumor cells. Collectively, the results suggest that augmentation of the therapeutic efficacy of irinotecan against colon cancer liver metastases by immunomodulation with JBT 3002 may be associated with elevated inducible nitric oxide synthase and endogenous interleukin-15 in tumor-infiltrating macrophages.

Adjuvants, Immunologic↗

PubMed1999

Effect of the immunomodulating agent, pentoxifylline, in the treatment of sepsis in prematurely delivered infants: a placebo-controlled, double-blind trial.

OBJECTIVE: To evaluate the influence of the methylxanthine derivative, pentoxifylline, on plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6 in prematurely delivered infants with generalized bacterial infections and to assess the effect of this immunomodulating drug on the clinical outcome in newborns with sepsis. DESIGN: A prospective, randomized, double-blind trial. SETTING: The neonatal intensive therapy units in university teaching hospitals. PATIENTS: One hundred patients with sepsis admitted during a 1.5-yr period. INTERVENTIONS: Patients were randomly assigned to receive pentoxifylline (pentoxifylline group) in a dose of 5 mg/kg/hr for 6 hrs on 6 successive days or an identically presented placebo (placebo group). MEASUREMENTS AND MAIN RESULTS: Only infants with sepsis confirmed by positive blood culture were recruited into the study. There were no significant differences at randomization between the pentoxifylline and placebo groups with regard to the birth weight, gestational age, gender, Apgar score, hypotension, neutropenia, thrombocytopenia, metabolic acidosis, plasma levels of cytokines, and occurrence of shock. Plasma levels of TNF, IL-1, and IL-6 were evaluated before and after the drug or placebo administration on the first, third, and sixth days of therapy. Cytokines were determined by immunoenzymetric test EASIA (TNF) and Endogen Interleukin-Elisa (IL-1, IL-6). The frequency of gram-negative sepsis was similar in both groups (37.5% and 36.8%). Pentoxifylline significantly diminished plasma TNF levels (p = .009) but had no effect on plasma IL-1 levels. Mean plasma IL-6 levels, which were measured in the pentoxifylline group on the 6th day of the study, were significantly lower compared with respective data obtained in the placebo group. Only 1 of 40 infants with sepsis in the pentoxifylline group died, whereas 6 of 38 infants in the placebo group did not survive (p = .046). An increased incidence of disordered peripheral circulation and metabolic acidosis (p = .048), anuria or oliguria (p = .03), disseminated intravascular coagulation (p = .043), and the occurrence of clinical symptoms of necrotizing enterocolitis (p = .025) was observed in the course of sepsis in infants in the placebo group. CONCLUSION: Pentoxifylline significantly affects the synthesis of TNF and IL-6 as well as reduces the mortality rate in premature infants with sepsis. The dosage and schedule of drug administration in this study attenuated the severity of the clinical course of sepsis in this group of patients.

Adjuvants, Immunologic↗

PubMedDate not supplied

An evaluation of cyclophosphamide as an immunomodulator in multiple septic animal models.

Cyclophosphamide has shown promise as an immunomodulator in early animal trials involving mice and guinea pigs. To test the effectiveness of this agent in a rat model, 268 adult Lewis rats were subjected to a 30% total body surface area burn and were challenged with Pseudomonas aeruginosa 1244 administered intraperitoneally on postburn day 1 or 4, or painted on the burn wounds on postburn day 1. The animals were then followed up to determine mean survival times and survival rate percentages. Cyclophosphamide was administered to the animals on postburn days 0, 2, and 4 at a dose of either 0.5, 1.0, 5.0, or 15.0 mg/kg. A final group received saline. None of the doses significantly prolonged survival in any of the septic models, and the 15 mg/kg dose significantly shortened it in all three models. Thus, the beneficial immunomodulatory effects previously seen in mouse and guinea pig models were not seen in the rat model. Further animal investigations would appear to be indicated before human studies are undertaken.

Animals↗

PubMed2001

Immunomodulation of glioma cells after gene therapy: induction of major histocompatibility complex class I but not class II antigen in vitro.

OBJECTIVE: Acquired immunity has been demonstrated in Fischer rats bearing syngeneic 9L tumors after herpes simplex virus (HSV) thymidine kinase (TK) gene transfection and ganciclovir treatment. The nature of this immunity in rats and its relevance to the HSV TK/ganciclovir protocol for human subjects remain to be determined. In this study, levels of major histocompatibility complex (MHC) Class I and II antigen expression were measured before and after HSV TK transfection, in an effort to document immunomodulatory changes caused by gene therapy. METHODS: Tumor cells from the 9L gliosarcoma cell line, three primary human glioma cultures, and the human glioma cell line U87 MG were transduced with HSV TK vector-containing supernatant from fibroblast-producing cells (titer of 5 x 10(6) colony-forming units/ml) and selected in G418 medium for neomycin resistance. Clones were pooled or individually selected for cell-killing assays with ganciclovir, to confirm TK expression (10(3) cells/well in a 96-well dish). Northern analyses using MHC Class I and Class II complementary deoxyribonucleic acid probes were performed on blots containing total ribonucleic acid from wild-type tumor cells and HSV TK transfectants. A beta-actin complementary deoxyribonucleic acid probe served as an internal control. Cell surface expression was confirmed with flow cytometry. The induction of MHC Class I was tested for cycloheximide and genistein sensitivity. RESULTS: All cell cultures exhibited increases in MHC Class I but not MHC Class II expression, as determined by Northern analysis densitometry and flow cytometry. Cycloheximide treatment did not diminish the up-regulation of MHC Class I after retroviral transfection, implicating a signal transduction pathway that does not require ongoing protein synthesis. Genistein pretreatment of cell cultures did diminish the up-regulation of MHC Class I, implicating a tyrosine kinase in the signaling cascade. CONCLUSION: Induction of MHC Class I in rat and human glioma cells after HSV TK retroviral gene therapy is a primary effect that is dependent on tyrosine kinase activity. Specific immune responses generated after transfection may represent an important general side effect of gene therapy protocols. Elucidation of the mechanism of immunomodulation after gene therapy will likely yield safer and more effective clinical protocols.

Animals↗

PubMed2001

Immunomodulators.

Cytokine immunomodulators have received considerable attention. Interferon-alpha has broad clinical application for treatment of a number of viruses. The neutrophil-stimulatory effects of interferon-gamma are useful in neutrophil disorders. TNF antagonists are useful in rheumatoid arthritis but carry the risk of activating intracellular organisms. Hemopoietic growth factors have considerable clinical effect in patients receiving immunosuppressive chemotherapy. A number of cytokines and cytokine antagonists are undergoing research development.

Adjuvants, Immunologic↗