Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of IL-12 on a murine model of allergic lung inflammation. Administration of IL-12 was timed to interfere with either allergic sensitization (early dosage) or the hypersensitivity inflammatory response in the lung (late dosage), or both (early and late dosages). Comparisons of IL-12- and PBS-treated animals within each treatment group revealed several noticeable effects of IL-12. Early dosage, and the combination of early and late dosages, strikingly decreased ragweed-specific serum IgE, tracheal ring reactivity to acetylcholine, and BAL eosinophilia following allergen challenge. In contrast, late dosage had no effect on IgE levels and only a minimal effect on tracheal ring reactivity, but had a modest effect on recruitment of eosinophils. Early dosage down-regulated IL-5 and IL-10, but did not alter IL-4 or IFN-gamma expression. Late dosage down-regulated IL-5, up-regulated IL-10 and IFN-gamma, but did not change IL-4 expression. The combination of early and late dosage down-regulated IL-4, IL-5, and IL-10 expression, but increased IFN-gamma expression and production in the BAL cells and fluids. Taken together, these results indicate that IL-12 has potent immunomodulatory effects on allergic lung inflammation that depend on the timing of IL-12 administration relative to allergic sensitization and allergen challenge.
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PMID:Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses. 889 55

Chronic relapsing experimental autoimmune encephalomyelitis (EAE), induced in mice by the injection of myelin basic protein (MBP), is a T cell-mediated autoimmune disease characterized by periods of paralysis and remission. We have shown previously that the oral administration of MBP or MBP peptides renders Lewis rats refractory to EAE. This study was undertaken to examine the conditions necessary to produce oral tolerance in a chronic relapsing model of EAE in B10.PL mice. The optimal tolerizing regimen for the mouse was found to be a single feeding of 20 mg of MBP suspended in PBS. To determine the ability to suppress chronic disease, a range of doses (0.4-100 mg) was administered orally in a single dose before challenge. Larger oral doses (20 or 100 mg) of MBP provided the best protection from EAE, while 0.4 mg exacerbated the clinical course of disease. Secretion of the proinflammatory cytokines, IL-2 and IFN-gamma, were lowest in the group fed 20 mg. A single feeding of MBP before challenge or as late as the first day of clinical signs showed significant protection over the relapsing disease course. Once relapsing EAE was established, multiple oral doses of MBP were required to achieve suppression of clinical signs of disease. These findings suggest that vehicle, dosage, and timing are important considerations in the successful application of oral tolerance strategies for suppression of chronic disease processes.
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PMID:Suppression of murine chronic relapsing experimental autoimmune encephalomyelitis by the oral administration of myelin basic protein. 889 61

Nasal administration of nicotinic acetylcholine receptor (AChR) to Lewis rats prior to myasthenogenic immunization with AChR plus Freund's complete adjuvant (FCA) resulted in prevention or marked decrease of the severity of EAMG, suppression of AChR-specific B cell responses and of AChR-reactive T cell functions. To examine the involvement of immunoregulatory cytokines and the underlying mechanisms involved in tolerance induction, in situ hybridization with radio-labelled synthetic oligonucleotide probes was adopted to enumerate mononuclear cells (MNC) expressing mRNA for the proinflammatory cytokine IFN-gamma, the B cell stimulating IL-4 and the immune response-down-regulating TGF-beta. Popliteal and inguinal lymph nodes from EAMG rats contained elevated numbers of AChR-reactive IFN-gamma, IL-4 and TGF-beta mRNA-expressing cells compared with control rats receiving PBS nasally and injected with FCA only. Nasal tolerance to EAMG was accompanied by decreased numbers of AChR-reactive IFN-gamma and IL-4 mRNA-expressing cells, and strong up-regulation of TGF-beta mRNA-positive cells in lymphoid organs compared with non-tolerized EAMG control rats. The relative affinity of anti-AChR antibodies was lower, but muscle AChR amounts were higher in nasally tolerized rats compared with non-tolerized EAMG control rats. The results suggest that IFN-gamma and IL-4 are central effector molecules in the development of EAMG, and that TGF-beta plays an important role in tolerance induction to EAMG.
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PMID:Cellular mRNA expression of interferon-gamma (IFN-gamma), IL-4 and transforming growth factor-beta (TGF-beta) in rats nasally tolerized against experimental autoimmune myasthenia gravis (EAMG). 909 37

There is substantial evidence for interactions between the immune and endocrine systems at different levels. In the present study we investigated whether human growth hormone (hGH) could stimulate proliferation of interferon-gamma-secreting cells (IFN-gamma-SC), and production of IFN-gamma. Human peripheral blood mononuclear cells (PBMC) taken from 15 normal subjects were incubated with varying doses (200,400,600 and 800 ng/ml) of recombinant hGH. Samples of cells were also incubated with PBS buffer (without hGH) to serve as controls. Effects of hGH were studied by enumerating IFN-gamma-SC and by measuring the concentration of IFN-gamma using an Immunospot assay and an enzyme-linked immunosorbent assay, respectively. The results showed that hGH significantly increased both the number of IFN-gamma-SC and the concentration of IFN-gamma in a dose-dependent manner. The maximum effects were obtained in the presence of (400 ng/ml) hGH (15 +/- .5 IFN-gamma-SC/10(6) PBMC and 300 +/- 55 U/ml IFN-gamma) compared to controls (4 +/- 2 IFN-gamma-SC/10(6) PBMC and 50 +/- 10 U/ml IFN-gamma). The results of the present study suggest that hGH might influence the immune system by stimulating the proliferation of IFN-gamma-SC and the production of IFN-gamma.
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PMID:Growth hormone stimulates production of interferon-gamma by human peripheral mononuclear cells. 919 4

The regulatory functions of IL-12 on granuloma formation by the eggs of S. japonicum in the lungs of BALB/c mice were studied. Mice were injected i.v. with the eggs to induce the pulmonary granuloma. On days 0, 1, 2, 3, 7, 8 after injection, mice were injected i.p. with murine rIL-12 at a dose of 1 microgram day-1 (Group I) or 3 micrograms day-1 (Group II) or with PBS as a control (Group III). On day 10, all mice were sacrificed. The areas of pulmonary granulomas in histological sections were quantitatively measured by image analyser and the levels of mRNA for IL-10, IFN-gamma, IL-12 and IL-5 were assayed by reverse transcriptase PCR (RT-PCR). The results showed that the mean area per granuloma was significantly decreased in Groups I and II as compared with Group III. As for cytokine induction, IL-10- and IFN-gamma-specific bands appeared in Groups I and II, but not in Group III. Bands for IL-5 appeared in all groups, while bands for IL-12 were not detected in any group. It is suggested that IL-12 could inhibit the Th2 dominant granuloma formation induced by the eggs of S. japonicum.
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PMID:Effect of IL-12 on granuloma formation induced by injected Schistosoma japonicum eggs. 927 91

It has recently been found that in systemic lupus erythematosus (SLE), a multisystem inflammatory disorder characterized by autoantibody production and decreased cellular immune response, increased spontaneous production of IL-10 occurs. The immunomodulator AS101 (ammonium trichloro(dioxoethylene-0,0')tellurate) was previously shown to significantly decrease IL-10 levels in cancer patients and in murine models. This study shows that AS101 inhibits the development of SLE-related autoimmune pathological manifestations. AS101 decreased the spontaneous IL-10 production by mononuclear cells from SLE patients in vitro. In vivo, systemic injection of AS101 to SCID mice transplanted with mononuclear cells from SLE patients significantly decreased serum human IL-10 levels. There was also a decrease in all serum human Ig isotypes, in anti-dsDNA, and in anti-Sm Igs. In the New Zealand Black/New Zealand White/F1 model, AS101 significantly increased serum TNF-alpha and IFN-gamma while decreasing IL-10 levels; these changes were accompanied by a rapid decrease in anti-dsDNA and anti-ssDNA Igs. More importantly, continuous treatment of New Zealand Black/New Zealand White/F1 mice with AS101 for 6 mo led to the development of proteinuria in 30% of the treated mice compared with 100% in PBS-treated mice (p < 0.001). AS101 treatment reduced the level of immmune complex deposition in the glomeruli, prevented glomerular hypercellularity and mesangial expansion and led to a much smaller mean glomerular volume in treated mice (185 +/- 6 vs 428 +/- 47.103 microm3; p < 0.01). We suggest that treatment with a nontoxic immunomodulator such as AS101, previously used in phase II trials on cancer patients, may be an effective therapeutic approach for controlling SLE.
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PMID:Delay in the onset of systemic lupus erythematosus following treatment with the immunomodulator AS101: association with IL-10 inhibition and increase in TNF-alpha levels. 930 Jun 85

This study explores nasal administration of myelin basic protein (MBP) as a potential means of inducing tolerance to relapsing experimental autoimmune encephalomyelitis (PR-EAE), an experimental multiple sclerosis (MS) model that was induced in DA rats by immunization with rat spinal cord homogenate and incomplete Freund's adjuvant. DA rats received a total dosage of 0, 6, 60, 600 micrograms/rat of bovine MBP on ten consecutive days prior to immunization. EAE with typical course was observed in control rats receiving only PBS nasally, and in rats receiving 6 micrograms/rat of MBP. Rats receiving 60 micrograms/rat of MBP developed acute EAE but no relapse during 60 days of observation post immunization (p.i.). Only one of eight rats receiving 600 micrograms/rat of MBP developed slight, transient EAE. This protection was confirmed at the histology level and was associated with decreased levels of MBP-reactive IFN-gamma secreting Th1-like spleen cells on day 13 and 60 p.i. Rats receiving 60 and 600 micrograms/rat of MBP showed decreased serum anti-MBP IgG2b antibody levels on day 60 p.i., and rats receiving 600 micrograms/rat of MBP had marginally increased anti-MBP IgG1 antibody levels in serum compared to control EAE rats. Cytokine mRNA profiles in central nervous system (CNS) and spleen mononuclear cells were evaluated. Dose-dependent reduction of TNF-alpha mRNA expression were observed both in CNS and in splenocytes. Increased IL-4 and TGF-beta mRNA expression were observed in CNS of low (6 micrograms/rat) and median (60 micrograms/rat) dose of MBP tolerized rats and in splenocytes of rats tolerized with 600 micrograms/rat of MBP. We conclude that nasal administration of MBP in DA rat prevents EAE induced by immunization with whole rat spinal cord homogenate that, besides MBP, contains multiple antigenic myelin proteins. A mechanism involving MBP-reactive regulatory cells expressing IL-4 and TGF-beta mRNA acts as part in the induction of this tolerance.
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PMID:Nasal administration of myelin basic protein prevents relapsing experimental autoimmune encephalomyelitis in DA rats by activating regulatory cells expressing IL-4 and TGF-beta mRNA. 941 60

We examined the effects of a newly identified cytokine, IL-18, originally designated as IFN-gamma-inducing factor, in a mouse model of pulmonary and disseminated infection with a highly virulent strain of Cryptococcus neoformans. Administration of murine rIL-18 enhanced elimination of live micro-organisms from the lungs, prevented fungal dissemination to the brain, reduced the level of serum cryptococcal capsular polysaccharide Ags, and increased the survival rate of infected mice. Histologic examination of lung sections of infected and PBS-treated mice showed a poor cellular inflammatory reaction and a large number of multiplying C. neoformans yeast cells in alveolar spaces. In contrast, massive infiltration of inflammatory cells, consisting mainly of mononuclear cells, characterized sections of lungs of infected animals treated with IL-18. Treatment with IL-18 also increased the level of serum IFN-gamma. In addition, the protective effect of IL-18 on cryptococcal infection was abrogated by administration of neutralizing anti-IFN-gamma mAb. Finally, we examined the effect of neutralizing anti-IL-18 Ab on cryptococcal infection to define the physiologic role of this cytokine in host defense using another weakly virulent strain of C. neoformans, which induced the expression of IL-18 mRNA in the infected lungs. Administration of this Ab exacerbated the infection, as shown by the increased lung burden. Our results indicate that IL-18 plays an important role in host defense against infection with C. neoformans.
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PMID:IL-18 protects mice against pulmonary and disseminated infection with Cryptococcus neoformans by inducing IFN-gamma production. 954 93

Allergic asthma is thought to be mediated by CD4+ T lymphocytes producing the Th2-associated cytokines, IL-4, and IL-5. Recently, the costimulatory molecules B7-1 and B7-2, which are expressed on the surface of APC, have been suggested to influence the development of Th1 vs Th2 immune responses. We examined the in vivo role of these costimulatory molecules in the pathogenesis of Th2-mediated allergen-induced airway hyperresponsiveness in a murine model of asthma. In this model, OVA-sensitized A/J mice develop significant increases in airway responsiveness, pulmonary eosinophilia, and pulmonary Th2 cytokine expression following aspiration challenge with OVA as compared with PBS-control animals. Strikingly, administration of anti-B7-2 mAb to OVA-treated mice abolished allergen-induced airway hyperresponsiveness, pulmonary eosinophilia, and elevations in serum IgG1 and IgE levels. Anti-B7-2 treatment of OVA-treated mice reduced both total lung IL-4 and IL-5 mRNA and bronchoalveolar lavage fluid IL-4 and IL-5 protein levels, with no significant changes in IFN-gamma message or protein levels. In contrast, treatment with anti-B7-1 mAbs had no effect on allergen-induced airway hyperresponsiveness, IgE production, or cytokine production, however, it significantly suppressed pulmonary eosinophilia. We conclude that B7-2 provides the necessary costimulatory signal required for the development of in vivo allergic responses to inhaled allergen exposure.
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PMID:Development of murine allergic asthma is dependent upon B7-2 costimulation. 955 45

We have demonstrated previously that susceptibility of murine strains to the development of allergic airway responses is associated with a type 2 cytokine pattern. In the present study, we examine the in vivo role of IL-12 in the immune response to allergen exposure in susceptible (A/J) and resistant (C3H/HeJ, C3H) strains of mice. OVA sensitization and challenge induced significant increases in airway reactivity in A/J mice as compared with their PBS-challenged controls, while no increases in airway reactivity were observed in OVA-challenged C3H mice. OVA exposure of A/J mice resulted in marked increases in the Th2 cytokines, IL-4 and IL-10, in the bronchoalveolar lavage fluid, whereas increases in IFN-gamma were observed in C3H mice. Strikingly, anti-IL-12 mAb (1 mg/mouse) treatment resulted in threefold increases in airway reactivity in OVA-challenged resistant C3H mice, concomitant with significant increases in bronchoalveolar lavage levels of Th2 cytokines and decreases in IFN-gamma. IL-12 depletion of C3H mice also suppressed OVA-specific serum IgG2a levels and increased both serum OVA-specific IgG1 and IgE levels. Blockade of endogenous IL-12 levels in susceptible A/J mice resulted in further augmentation of type 2 immune responses. These results demonstrate that endogenous production of IL-12 is essential for resistance to Ag-induced airway hyperresponsiveness, and furthermore, that dysregulation of IL-12 production may lead to the development of deleterious type 2 immune responses to inhaled allergens.
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PMID:Resistance to antigen-induced airway hyperresponsiveness requires endogenous production of IL-12. 967 Sep 70


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