Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “immune modulation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources
PubMed1995

Suppression of adult T cell leukemia-derived factor/human thioredoxin induction by FK506 and cyclosporin A: a new mechanism of immune modulation via redox control.

Adult T cell leukemia-derived factor (ADF), which is identical to a disulfide reducing enzyme human thioredoxin (TRX), is produced and released by activated or virus-infected lymphocytes. Here we report that, in peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA), ADF/TRX mRNA was induced within 8 h after stimulation as detected by in situ hybridization study. To analyze the mechanism of ADF/TRX induction during T cell activation, the effects of immunosuppressants including FK506, rapamycin (Rap) and cyclosporin A (CsA) on ADF/TRX expression were investigated by immunoblot analysis. ADF/TRX induction in PBMC by PHA, Con A or OKT3 mAb was almost completely suppressed by FK506. Whereas CsA also inhibited ADF/TRX expression in OKT3 mAb-stimulated PBMC, Rap failed to affect it in spite of exhibiting growth inhibition. In addition, exogenous IL-2 could not increase ADF/TRX production in FK506-treated PBMC or in PHA blasts. These results indicate that ADF/TRX induction in T cell activation depends on calcineurin-dependent events in the early phase and that IL-2 production is not directly involved in ADF/TRX induction. Furthermore, when recombinant ADF (rADF) was added to a culture of PBMC 1 h before the addition of PHA and FK506, the action of FK506 was partially reversed as determined by [3H]thymidine incorporation and viable cell counts. These results suggest that ADF/TRX produced and released from PBMC may be a crucial event in lymphocyte activation, and that FK506 and CsA may exert the immune suppression partly through inhibiting the induction of the endogenous reducing factor ADF/TRX.

Adjuvants, Immunologic↗
PubMed1997

Atopic dermatitis: immunobiology and treatment with immune modulators.

Atopic dermatitis (AD), a chronic inflammatory skin disease, is frequently seen in patients with a personal or family history of asthma and allergic rhinitis. Population studies suggest an increasing prevalence of AD in children since World War II, with 10-15% of the population being affected by AD at some time during childhood. In patients with moderate to severe AD, involvement can be life-long, causing significant interference with school, work and social interactions. The term atopic dermatitis was introduced to reflect the close association between AD and respiratory allergy. During the past decade, extraordinary progress has been made in our understanding of the immunopathogenesis of allergic diseases. In particular, this constellation of inherited illnesses has now been demonstrated to be associated with activation of a specific group of cytokine genes encompassing IL-3, IL-4, IL-5, IL-13 and granulocyte-macrophage colony-stimulating factor (GM-CSF). The molecular basis for selective activation of this cytokine gene cluster and the immunological consequences are now being pursued actively by many laboratories. However, it is clear that allergic diseases result from a polygenic inheritance pattern which involves not only cytokine gene activation but also activation of other less well defined gene products. Furthermore, the clinical expression of allergic diseases is highly dependent on a complex interaction between the host and its environment, e.g. allergen exposure. The genetic predisposition to develop allergic responses may be similar in patients with AD and other allergic diseases, such as asthma. However, targeting of the allergic immune response may relate to the organ in which allergen sensitization first occurs; the capacity of immune effector cells, e.g. T lymphocytes, to home preferentially to the skin versus the respiratory mucosa; and the programmed response of resident cells, e.g. epithelial cells, to injury and inflammation. This review examines the cellular and immunological mechanisms that are thought to play an important role in the pathogenesis of chronic AD. An understanding of the immunological basis of AD is likely to have important clinical implications in our approach to the management of this common illness, and the development of immunomodulators for its treatment.

Adjuvants, Immunologic↗
PubMed1987

[Clinical and immune-modulating effects of the treatment with unsaturated fatty acids in atopic dermatitis].

The metabolism of essential unsaturated fatty acids seems to show changes in patients with atopic dermatitis (AD). A defect or a deficiency of a Delta-6-Desaturase, which transforms cis-linoleic acid into gamma-linolenic-acid will be discussed. We examined the influence of a treatment with unsaturated fatty acids on clinical phenotype and the surface antigens of lymphocytes in peripheral blood. Prolonged recurrence free intervals as well as a faster ability to control relapse were established. Dysbalance in the lymphocytic system was able to be positively influenced. We found an increase of Leu 2 a-antigen carrying T-suppressor-lymphocytes and of the Leu 3+8+- antigen carrying subpopulation of T-helper-lymphocytes, which are responsible for activation of precursor T-suppressor cells into.

Adolescent↗
PubMed2001

Does leptin modulate immune and endocrine response in the time of LPS-induced acute inflammation?

OBJECTIVES: In many studies it has been reported, that leptin may play an important role not only in the regulation of food intake and body weight but can modify immune response. The aim of our study was to estimate the effects of the administration of exogenous leptin on serum concentration of proinflammatory cytokines (interleukin 6-IL 6 and tumor necrosis factor alpha-TNF alpha) and anti-inflammatory cytokine (interleukin 10 - IL 10) during LPS induced acute inflammation. We also estimated leptin's influence on pituitary, thyroid, adrenal and gonadal hormones in response to lipopolysaccharide (LPS) induced acute inflammation. METHODS: Male rats Wistar-Kyoto were divided into four groups, which received respectively: placebo (0.9% NaCl), LPS, leptin and leptin with LPS. The TNF alpha and IL 6 serum concentrations were measured after 2 hours and IL 10 after 4 hours. The pituitary, thyroid, adrenal and gonadal hormones serum concentrations were measured after 2 and 4 hours. Cytokine concentrations were estimated using ELISA tests and hormones concentrations using RIA tests. RESULTS: Leptin did not have an effect on both cytokine responses (proinflammatory and anti-inflammatory) in the time of LPS-induced acute inflammation. Leptin enhanced LPS-induced increasing of corticosterone secretion after 2 hours and decreased LPS-induced inhibition of testosterone secretion after 4 hours. CONCLUSIONS: Leptin can modulate hormone response during LPS-induced acute inflammation.

Animals↗
PubMed1994

Immune modulation during treatment of systemic sclerosis with plasmapheresis and immunosuppressive drugs.

Immunologic effects of our previously reported treatment protocol were determined in eight systemic sclerosis (SSc) patients treated with plasmapheresis, cyclophosphamide, and prednisone as tolerated. Prior to treatment total serum IgG and circulating lymphocytes including the percentage of B, T, and NK cells were normal. Peripheral blood lymphocytes showed evidence of activation by increased spontaneous proliferation and expression of CD25 on T cells. In addition, CD4+ T cells showed increased expression of both activation (HLA-DR) and maturation (CD29) markers. The percentage of CD8+ T cells was low, resulting in a high CD4:CD8 T cell ratio. During treatment all patients showed clinical improvement. Laboratory testing showed that their NK cells had declined by 81%, B cells declined by 96%, and serum IgG declined by 49%; high titer ANA were abrogated. Total T cells declined by 52%, and the CD4:CD8 ratio fell to normal, due to an almost twofold increase in the percentage of CD8+ T cells. Spontaneous lymphocyte proliferation increased further and was accompanied by increased maturation and activation of both CD4+ and CD8+ T cells, as well as a reduction of immature CD4+ T cells. Among CD8+ T cells the percentage of cytotoxic cells increased as shown by an increase in the CD11b-, CD38+, and CD29+ phenotypes, a finding confirmed on follow-up three-color flow cytometry which showed an increase in activated CD8 cells bearing the cytotoxic CD28 marker. Three-color cytometry also showed that cells with the CD4+CD45RA+CD31+ suppressor inducer phenotype were low and those with the CD4+CD45RO+ CD31- helper inducer phenotype were high in treated SSc patients. Deficient CD4+CD45RA+CD31+ and CD8+ T cell populations suggest an immune regulatory imbalance in SSc which could have led to CD4+ T cell activation and autoimmunity. Depletion of B cells, in conjunction with augmentation of cytotoxic CD8+ T cells through combined therapy, may have diminished the autoimmune response.

Adult↗
PubMed2001

Design and use of an inducibly activated human immunodeficiency virus type 1 Nef to study immune modulation.

The Nef protein of the human immunodeficiency virus type 1 (HIV-1) has been shown to enhance the infectivity of virus particles, downmodulate cell surface proteins, and associate with many intracellular proteins that are thought to facilitate HIV infection. One of the challenges in defining the molecular events regulated by Nef has been obtaining good expression of Nef protein in T cells. This has been attributed to effects of Nef on cell proliferation and apoptosis. We have designed a Nef protein that is readily expressed in T-cell lines and whose function is inducibly activated. It is composed of a fusion between full-length Nef and the estrogen receptor hormone-binding domain (Nef-ER). The Nef-ER is kept in an inactive state due to steric hindrance, and addition of the membrane-permeable drug 4-hydroxytamoxifen (4-HT), which binds to the ER domain, leads to inducible activation of Nef-ER within cells. We demonstrate that Nef-ER inducibly associates with the 62-kDa Ser/Thr kinase and is localized to specific membrane microdomains (lipid rafts) only after activation. Using this inducible Nef, we also compared the specific requirements for CD4 and HLA-A2 downmodulation in a SupT1 T-cell line. Half-maximal downmodulation of cell surface CD4 required very little active Nef-ER and occurred as early as 4 h after addition of 4-HT. In contrast, 50% downmodulation of HLA-A2 by Nef required 16 to 24 h and about 50- to 100-fold-greater concentrations of 4-HT. These data suggest that HLA-A2 downmodulation may require certain threshold levels of active Nef. The differential timing of CD4 and HLA-A2 downmodulation may have implications for HIV pathogenesis and immune evasion.

Animals↗
PubMed2003

Proteasome inhibitors: a novel tool to suppress human cytomegalovirus replication and virus-induced immune modulation.

Recently, we like others, demonstrated that systemic inflammation is the most important mechanism involved in (re)activation of human cytomegalovirus (HCMV) in both immunocompetent patients. By in vitro studies the eukaryotic transcription factor NF-kappaB could be identified as the key mediator of TNF-alpha- and IE1-dependent stimulation of the HCMV IE1/2 enhancer/promoter activity, which is crucial for initiation of viral gene expression during reactivation from latency as well as productive infection. The enzymatic proteasome complex plays a central role in regulating intracellular processes, including the activation of NF-kappaB. As present antiviral strategies target mainly late events in HCMV replication (DNA replication, virus assembly) that do not completely prevent virus mediated immunopathogenesis, we wondered whether proteasome inhibitors might be a novel tool for targeting the interaction between inflammation and HCMV (re)activation. Here, proteasome inhibitors like MG132, PSI, II and III (MG262) have been shown to block both TNF-alpha-associated up-regulation of the HCMV IE1/2 enhancer/promoter in monocytic cells in an in vitro transient transfection system and HCMV replication in permissive embryonal fibroblasts. Importantly, ganciclovir-resistant HCMV strains are sensitive to proteasome inhibitors. The effect of proteasome inhibitors on HCMV replication was found to be specific as replication of other herpes viruses, like HSV-1 and HSV-2, under identical experimental conditions was not influenced. Inhibition of HCMV replication correlated with a delayed and significantly reduced expression of IE proteins, particularly of the IE2 protein, suggesting that MG132 blocks HCMV replication at an immediate early stage of infection. Early and late protein synthesis as shown exemplary for the pp52 (DNA-binding protein) and p68 (structural protein) protein production and viral DNA synthesis were also inhibited. Suppression of HCMV replication could be correlated with an increased cytosolic accumulation of IkappaB as well as a reduced NF-kappaB binding activity in nuclear extracts of MG132-treated cells, which mainly regards NF-kappaB p50. MG132 also reduced the immune modulatory activity of the virus by abrogating virus-induced up-regulation of cellular ICAM-1. These data suggest that short-term therapy with proteasome inhibitors might be an alternative strategy to prevent (re)activation, replication and immune modulatory activity of HCMV in patients with systemic inflammation.

Chemokine CCL5↗
PubMed1993

[Clinical effects of blood transfusion-associated immune modulation on outcome of tumor surgery].

Extended experimental studies revealed different immunological mechanisms which are possibly responsible for blood transfusion-associated immunosuppressive conditions. To expect a clinical impact of these mechanisms on the course of tumor disease, it is necessary to postulate (1) that immunological mechanisms have a significant role in controlling tumor growth and (2) that blood transfusion-induced immunmodulation is long lasting. Both postulates are supported by recent reports and are the rationales of clinical studies indicating that blood transfusion is a risk factor for postoperative infections and tumor recurrence. Since all studies have been retrospective or uncontrolled, we performed a prospective controlled study in randomized groups of patients suffering from colorectal cancer and compared the effects of allogeneic and autologous blood transfusions. The results indicate that patients treated with allogeneic blood transfusion had significantly higher rates of postoperative infectious complications than patients who received autologous blood. Our preliminary follow-up observations found a trend towards higher tumor-free survival in patients treated with autologous blood which is statistically significant in subgroup analysis.

Adult↗
PubMed1997

A cytokine switch induced by human seminal plasma: an immune modulation with implications for sexually transmitted disease.

The immunosuppressive activity of human seminal plasma may be one factor in the aetiology of sexually transmitted disease and could be particularly important for the spread of human immunodeficiency virus (HIV). The advent of virus that can preferentially infect Langerhans cells of the genital mucosa underscores the relevance of seminal plasma effects. Virally infected cells are eradicated by the killing activity of T cells and natural killer (NK) cells and this cytotoxicity is stimulated by IL-12 (previously known as natural killer cell stimulatory factor) and partly inhibited by IL-10 (previously known as cytokine synthesis inhibitory factor). We have examined the effects of human seminal plasma on the production of these key cytokines. Cytokine production was measured in rapidly diluted, fresh, lipopolysaccharide (LPS)-stimulated, whole blood since this provided leukocytes with minimal exposure to prostaglandin. Prostaglandin concentrations and cytokine release were measured by ELISA. Addition of human seminal plasma diluted up to 100,000 times (0.001%) to blood cell cultures led to a marked increase in the IL-10/IL-12 ratio (P <0.02). A dose-dependent increase in the ratio was observed in five separate experiments, from a control value of 1 (no seminal plasma) to a mean value of 80 (1% seminal plasma). This cytokine switch was also seen when seminal plasma was substituted by pure prostaglandin E (PGE) and 19-OH PGE (the main prostaglandin constituent of human seminal plasma). Lipid-extracted seminal plasma was considerably less active at high dilutions than whole seminal plasma at the same dilution. However, its activity could be restored by the addition of synthetic PGE and 19-hydroxy PGE. A stimulation of IL-10 and a decrease in IL-12 in host-defence cells of the lower female reproductive tract will seriously affect the ability of cytotoxic T cells and NK cells to recognise and destroy virally infected cells. In addition, the stimulation of IL-10 will inhibit the release of the anti-HIV activity from CD8+ve cells. The cytokine switch reported here, activated by semen deposition, would exercise a key inhibitory control over vital immune defences in the lower genital tract, with ablation of cell-mediated responses and immunosurveillance.

Female↗
PubMed1989

Very low dose danazol in idiopathic thrombocytopenic purpura and its role as an immune modulator.

Danazol, an attenuated androgen, has been used successfully at its conventional dose (400-800 mg/day) in the treatment of idiopathic thrombocytopenic purpura (ITP). To minimize side effects, the authors tried a very low dose (50 mg/day) regimen which has not been used in any other disease and observed its efficacy in ITP. Fifteen patients were given this dosage of danazol. Its effects on T-cell subsets, B cells, and blastogenic response to pokeweed mitogen (PWM) and staphylococcus aureus (Staph A) were studied before and during therapy. The percentage of CD3 and the percentage and numbers of CD4 were significantly increased during therapy. Responses to PWM, a T-cell dependent B cell mitogen, were also significantly elevated during therapy. However, no change in the percentage of B (CD19) lymphocytes and response to Staph A, a polyclonal B cell mitogen, were noted. There were seven excellent-good and eight fair-poor responses in platelet counts. The excellent-good responders were found to have a more stable CD4 subset between before and during therapy compared to the fair-poor responders (p less than 0.05, Fisher's exact test). Very low dose danazol regimen, therefore, produced a significant increase in the CD4 without affecting the B cells. However, the excellent-good responder patients showed no significant increase in the CD4 lymphocytes.

Adult↗
PubMed2004

Immune modulation with a staphylococcal preparation in fibromyalgia/chronic fatigue syndrome: relation between antibody levels and clinical improvement.

The aims of this study were to evaluate the serological response to treatment with staphylococcal vaccine in fibromyalgia/chronic fatigue syndrome patients and to explore the relationship between serological response and clinical effect. Twenty-eight patients, half of whom served as controls, were recruited from a 6-month randomised trial in which repeated administration of the staphylococcal toxoid vaccine Staphypan Berna (Berna Biotech, Switzerland) was tested against placebo. Antibody status against extracellular toxins/enzymes, cell-wall components, and enterotoxins was evaluated at baseline and at endpoint. The clinical response to treatment was recorded in rating scales. In the group receiving active treatment, significant serological changes were recorded, whereas no significant changes were found in controls. Treatment led to a significantly increased capacity of serum to neutralise alpha-toxin and a significant increase in serum IgG to alpha-toxin and lipase. Furthermore, the increase in these parameters combined paralleled the improvement in clinical outcome. Thus, the greater the serological response, the greater was the clinical effect. In conclusion, this explorative study has shown that repeated administration of the Staphypan Berna vaccine in patients with fibromyalgia/chronic fatigue syndrome causes a serological response to several staphylococcal antigens, particularly to certain extracellular toxins and enzymes. The results further show that this response is related to the clinical outcome of treatment.

Adult↗
PubMed1991

Immune modulation in the guinea pig using cortisone acetate.

Cortisone acetate was administered to a group of guinea pigs (Cavia porcellus) at 0 (control), 20 (low) or 200 (high) mg/kg. Steroid was given daily for two individual 7 day periods, separated by 7 days of no treatment. The effects of this steroid on body weight gain, thymic weight, total and differential leukocyte counts, serum antibody titer against a bacterin, dermal hypersensitivity response to a sensitizing agent and histological evaluation of lymphoid and other tissues were evaluated. Significant differences in body weight gain (p less than 0.05) and thymic weight (p less than .01) were noted. For total leukocyte count, no significant difference among treatment groups at individual time points was noted (p greater than .10), while significant differences were seen in lymphocyte and neutrophil counts (p less than .01). A significant difference in antibody titer among the treatment groups was observed (p less than .01). For the dermal hypersensitivity response, there was no consistent pattern among the treatment groups in gross (macroscopic) skin reactions. Microscopically, differences were seen in the inflammatory response among the treatment groups. Histologically, steroid related changes were seen in thymus, spleen, lymph node and liver. At necropsy, 24 of 40 animals had lesions of focal necrotizing hepatitis. Three affected animals died and remaining animals showed no clinical illness. The cause of the necrotizing hepatitis could not be determined by culture, special stains, electron microscopy, serology or by attempts at transmission with affected liver samples.

Animals↗
PubMed2003

Use of mouse models to evaluate the persistence, safety, and immune modulation capacities of lactic acid bacteria.

Recent clinical and experimental observations showed that specific probiotic microorganisms may provide therapeutic benefits in inflammatory bowel disease. However, a rigorous screening for new candidate probiotic strains with optimized therapeutic properties necessitates also determining possible adverse interactions with the host, particularly in individuals who are not healthy. We have evaluated the persistence of strains of lactic acid bacteria (LAB) in the digestive tracts of mice, their immunomodulation capacity, and their safety in healthy animals and in a colitis model. Following daily administration of 10(9) CFU of viable LAB orally, intragastrically, or intrarectally, the animals' feces were examined for bacterial excretion and cytokines were quantified in intestinal samples by quantitative reverse transcription-PCR. The level of bacterial translocation was assessed in healthy mice and in mice suffering from colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Irrespective of the route of administration, the potential probiotic strain Lactobacillus plantarum NCIMB8826 was found to persist for up to 10 days in the digestive tracts of mice. This strain did not induce detrimental effects in healthy or in TNBS-treated animals, as was reflected by the absence of weight loss, intestinal inflammation, modification of cytokine levels in the ileum and colon (healthy mice), and bacterial dissemination (healthy and colitic animals). Moreover, the translocation of endogenous microflora to the mesenteric lymph nodes and spleen was greatly reduced in the TNBS-treated mice after administration of LAB. This property, together with the strain's persistence capacity and innocuousness renders L. plantarum NCIMB8826 an attractive candidate as a probiotic to be used in the prevention or treatment of chronic inflammation.

Administration, Oral↗
PubMed1998

Effect of hypoxia on the hematopoietic and immune modulator preprotachykinin-I.

OBJECTIVES: To determine the effect of hypoxia on bone marrow mononuclear cells (BMMCs) and their ability to proliferate into granulocyte-macrophage colony-forming units (CFU-GMs) and erythroid burst-forming units (BFU-Es) and to determine the role of the neuroimmune and hematopoietic mediator, substance P. DESIGN: Controlled in vitro study. SETTING: University research laboratory. MATERIALS: Bone marrow aspirates were obtained from the posterior iliac crests of healthy volunteers after obtaining informed consent. INTERVENTIONS: The BMMCs were divided into the following groups: (1) normoxia, (2) two hours of hypoxia, and (3) six hours of hypoxia. Additional BMMCs were purified before the period of hypoxia, while others were incubated with neurokinin (NK) receptor antagonists. In other experiments, bone marrow stroma was grown to confluence and randomized to the following groups: (1) normoxia, (2) hypoxia, (3) normoxia and interleukin (IL) 1, and (4) hypoxia and IL-1. All groups were cultured for 2, 6, 12, or 24 hours. MAIN OUTCOME MEASURES: The formation of CFU-GMs and BFU-Es was measured after 10 to 14 days of incubation of the BMMCs. The messenger RNA of the preprotachykinin-I (PPT-I) gene and the NK-1 and NK-2 receptors was detected by using semiquantitative reverse transcriptase-polymerase chain reaction or Northern blot analysis on bone marrow stroma. The immunoreactivity of substance P in bone marrow stroma was measured by competitive enzyme-linked immunosorbent assay. RESULTS: Hypoxia resulted in a 110% increase in the number of CFU-GMs and a 78% increase in the number of BFU-E colonies at 6 hours (both P<.05). Elimination of the stromal elements by purification abrogated the increase in colony formation to nonhypoxic levels. Hypoxia induced PPT-I gene expression at 24 hours; however, no PPT-I expression was found in the hypoxic group incubated with IL-1. The receptor, NK-1, was found to be equal in both hypoxic groups; NK-2 was found to have a 4-fold increase in the hypoxia and IL-1 group over the hypoxia alone group and normoxia and IL-1 group. The levels of substance P immunoreactivity were found to be similar in all groups. Incubation of BMMCs with NK receptor antagonists to NK-1 alone or NK-1 and NK-2 decreased the number of CFU-GM and BFU-E colonies similar to the level in controls. CONCLUSIONS: These results indicate that hypoxia has a role in the proliferation and control of CFU-GMs and BFU-Es. This control seems to be mediated through the bone marrow stroma and modulated by NK receptors and induction of PPT-I. The neuropeptide, substance P, probably has a role but is clearly not the only mediator involved.

Cell Hypoxia↗
PubMed1980

Cellular immune modulation after a single high dose of Levamisole in patients with carcinoma.

The effect of a single high dose of Levamisole (200 mg/M2) on delayed-type hypersensitivity (DTH) in vivo and on lymphocyte blastogenesis to mitogens and antigens in vitro was studied in 26 patients with carcinoma. Similar studies were conducted in 24 control patients. Levamisole had a moderate but significant enhancing effect on DTH to Dermatophytin detectable no earlier than eight hours and still present at 48 hours after the drug administration. A moderate but significant enhancing effect on lymphocyte blastogenesis to mitogens and antigens was also demonstrated during the same time sequence. Further clinical trials with Levamisole should be conducted with more attention paid to schedule of drug administration.

Breast Neoplasms↗
PubMed1984

Immune modulation of a T-suppressor cell lymphoma by thymic humoral factor, a thymic hormone.

Lymphoid cells obtained from a mediastinal mass and bone marrow as well as peripheral blood of a patient with poorly differentiated diffuse malignant lymphoma were found to have both E and complement receptors. Addition of the bone marrow lymphoblasts to normal human T-lymphocytes induced a suppression of normal T functional activity as measured by a local xenogeneic graft versus host reaction. Incubation of the same cells with thymic humoral factor (THF), a thymic hormone, reversed their functional activity from suppression to help. Control studies with normal T-suppressor lymphocytes also showed a reversal of function to helper activity upon incubation with THF. In studies of normal T-lymphocytes with monoclonal antibodies, incubation with THF induced no change in phenotype in either theophylline-sensitive (suppressor) cells or theophylline-resistant (helper) cells. The ability of THF to modulate helper and suppressor activities suggests that this or similar agents may provide a useful means of therapy for disorders of immunoregulation.

Adult↗
PubMed2005

Immune modulation of collagen-induced arthritis by intranasal cytokine gene delivery: a model for the therapy of rheumatoid arthritis.

OBJECTIVE: To develop a passively targeted, patient-compliant, intranasal interleukin-10 (IL-10) gene therapy delivery system and to investigate its therapeutic benefit in experimental collagen-induced arthritis, a model of rheumatoid arthritis. METHODS: Arthritis was induced in DBA/1 mice and monitored following intranasal administration of an IL-10 plasmid (pG-IL-10) or the empty vector 2 days (days -2 and 19) prior to collagen injection (prophylactic group, as a single dose after collagen boost on day 21 (early therapy group, or as a single dose upon acquisition of a disease score of 3 (late therapy group. IL-10-induced alterations in cytokine secretion and proliferation by spleen and lymph node cells were assessed on days 31 and 65 and correlated with histologic changes and bone erosions assessed on day 65. RESULTS: Intranasal delivery of pG-IL-10 significantly delayed arthritis onset and reduced disease severity in the prophylactic group and early therapy group, reduced cellular infiltration and bone loss in the early therapy group, and reduced T cell proliferation in response to collagen on days 31 and 65 in these two groups, with a significant reduction in tumor necrosis factor alpha production on day 65. Within the late therapy group, disease progression was arrested for the rest of the study. The intranasally administered pG-IL-10 targeted monocytes and macrophages and showed dissemination to inflamed joints and draining lymph nodes in vivo. Importantly, systemic levels of IL-10 (in serum) were transient (peaking on day 2) and undetectable by day 4. CONCLUSION: Intranasal IL-10 gene delivery significantly reduces bone destruction, shows evidence of reducing joint inflammation, and may be mediated by high local levels of IL-10 produced by transfected monocytes trafficking to inflamed joints and draining lymph nodes.

Administration, Intranasal↗
PubMed1995

Granulocyte-macrophage colony-stimulating factor modulates immune function and improves survival after experimental thermal injury.

Thermal injury is associated with reduced colony-stimulating activity, which correlates with increased susceptibility to infection. To assess the effect of therapeutic administration of granulocyte-macrophage colony-stimulating factor (GM-CSF), 8-week old anaesthetized mice were subjected to either a 20 per cent body surface burn or a sham burn. Animals were subsequently treated with either vehicle or a range of doses of GM-CSF (10-1000 ng) with or without indomethacin (5 micrograms). Sepsis was induced by caecal ligation and puncture on day 10 after injury. Survival was significantly better in animals treated with 200 ng GM-CSF on days 5-9 after the burn. Concanavalin A-stimulated T cell proliferation and interleukin (IL) 2 production were significantly depressed after burn injury. In vivo therapy with 200 ng GM-CSF, however, led to a significant improvement in both of these parameters of T cell function. These data suggest that GM-CSF has a potential therapeutic role in the prevention of death from burn sepsis and appears to act, at least in part, by restoring defective T cell proliferation and IL-2 production.

Animals↗