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Context: Atopic dermatitis is a common chronic inflammatory skin disease affecting up to 20% of children and 1% of adults worldwide. Treatment of atopic dermatitis include corticosteroids and immunosuppressants, such as calcineurin inhibitors and methotrexate. However, these treatments often bring about adverse effects including skin atrophy, osteoporosis, skin cancer, and metabolic syndrome. Objective: In this study, we evaluated the therapeutic effects and mechanisms of sclareol, a natural diterpene, on atopic dermatitis (AD)-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) in mice. Materials and methods: To evaluate the effect of sclareol in vivo model, BALB/c mice were repeatedly injected intraperitoneally with sclareol (50 and 100 mg/kg) in 2,4-dinitrochlorobenzene (DNCB)-induced AD-like murine model. Major assays were enzyme-linked immunosorbent assay, histological analysis, flow cytometry, western blot analysis. Results: Intraperitoneal administration of sclareol (50 and 100 mg/kg) significantly attenuated AD-like symptoms, such as serum IgE levels, epidermal/dermal hyperplasia, and the numbers of infiltrated mast cells. In addition, systemic sclareol treatments reduced local pro-inflammatory cytokine concentrations, including IL-6, IL-1b, TNF-a, IL-4, IFN-g, and IL-17A, on AD-like lesions. Furthermore, we demonstrated that sclareol also suppressed T cell activation and the capability of cytokine productions (IFN-g, IL-4 and IL-17A) in response to DNCB stimulation. By examining the skin homogenate, we found that sclareol inhibited the AD-like severity likely through suppressions of both NF-kB translocation and phosphorylation of the MAP kinase pathway. Discussion and conclusions: Cumulatively, our results indicate that sclareol induced anti-inflammatory effects against the atopic dermatitis elicited by DNCB. Thus, sclareol is worth of being further evaluated for its potential therapeutic benefits for the clinical treatment of AD. [ABSTRACT FROM AUTHOR]

Context: Alum is thought to induce inflammation resulting in the release of danger signals such as uric acid (UA) which in turn enhances the immune response to an antigen. Hydrogen peroxide (H2O2) is produced as a byproduct in the purine catabolic pathway that leads to the production of UA. In addition, serum nitric oxide (NO) levels are increased in inflammation. Objective: To further explore the mechanism of action of alum, this study was designed to determine the effects of catalase and 1400W on the number of interleukin-4 (IL-4) and interferon-γ (IFN-γ) secreting spleen cells in mice given ovalbumin (OVA) with alum. Materials and methods: Groups of BALB/c mice were injected intraperitoneally with alum + OVA, alum, OVA, catalase, or 1400W. Other groups were treated with catalase or 1400W and given alum + OVA. The number of IL-4 and IFN-γ secreting spleen cells were determined at days 4 and 7 postinjection by enzyme-linked immunosorbent spot (ELISPOT). Results: Catalase and 1400W caused a decrease in the number of IL-4 secreting spleen cells induced by alum + OVA. 1400W caused a decline in the IFN-γ secreting spleen cells induced by alum + OVA. Catalase caused an increase in IFN-γ secreting spleen cells. Discussion and conclusion: It appears that H2O2 and NO are needed for alum-induced production of a T-helper 2 cytokine. NO also appears to be needed, whereas H2O2 appeared to inhibit an alum-induced production of a T-helper 1 cytokine. These results might explain why alum is mainly a promoter of a T-helper 2 response. [ABSTRACT FROM AUTHOR]

The objective of this study was evaluate the effect of coplanar polychlorinated biphenyls (PCB) 118-congener (PCB like-dioxin) and noncoplanar PCB 153-congener (PCB no like-dioxin) on differentiation of humans T-CD4+ lymphocytes into Th1 or Th2 subpopulations. Peripheral blood mononuclear cells (PBMC) were isolated from healthy volunteers (aged 25-30 years); T-CD4+ lymphocytes were separated from PBMC. Then, the differentiation of T-CD4+ cells into Th1 or Th2 subpopulation was performed and the intracellular cytokines analyses were assessed. No effect on IFNγ (produced by Th1 cells) production was observed when the cells were treated with both PCBs congeners. However, the PCB 118-congener induced an increase of IL-4-producing T-CD4 cells (produced by Th2 cells), PCB153 not exerted any effect on IL-4 production. The clinical significance of our data is uncertain, therefore, more studies are necessary in order to elucidate the effects generated in exposed human individual. [ABSTRACT FROM AUTHOR]

We evaluated the capacity of peripheral CD4+ T helper cells in four Common Variable Immunodeficiency (CVI) patients to secrete interleukin-4 (IL-4) and IL-5. While in control CD4+ T cells, stimulated via CD3 and cultured in presence of IL-2 or IL-15, a 10 fold increased production of IL-5 (146 ± 30; 142 ± 25 pg/ml) was found, a 4 fold increment of this cytokine was, instead, detected in 3 out of 4 CVI patients (34 ± 13; 39 ± 12 pg/ml) (p < 0.05). In conclusion, the reduction of IL-5, involved in the late regulation of B cell differentiation into Ig-secreting plasma cells, may contribute to the defective antibody production in CVI patients. [ABSTRACT FROM AUTHOR]

The mushroom Phellinus linteus (PL) has been shown to have antitumor and immunostimulatory effects. We hypothesized that the hot water extract of PL (WEPL) exerts its significant immunostimulatory effect by inducing production of the Th1-derived cytokine interferon-γ (IFN-γ) by T lymphocytes. T lymphocytes were isolated from the mice fed with 200 mg/kg of WEPL once a day for 4 weeks and then stimulated with the mitogen concanavaline A (Con A). IFN-γ gene and intracellular protein expressions were analyzed by RT-PCR and flow cytometry, respectively. The production of IFN-γ was measured by enzyme-linked immunosorbent assay. WEPL significantly enhanced the transcription of IFN-γ mRNA. The effect of WEPL on IFN-γ expression was further supported by a concomitant increase in the number of cells with intracellular IFN-γ protein as well as the secretion of IFN-γ. However, WEPL did not modulate either gene expression or protein secretion of interleukin-4, a Th2-associated cytokine, by Con A-stimulated T lymphocytes. Our results demonstrate that one of the potentially beneficial antitumor and immunostimulatory effects of WEPL may be mediated through the enhancement of IFN-γ secretion by T lymphocytes. [ABSTRACT FROM AUTHOR]

The production of IL-2 and IL-4 by thymocytes, spleen and axillary lymph node lymphocytes from female and male mice exposed to airborne suspended matter (ASM) was the scope of our investigations. Cytokines production by activated lymphocytes was determined by the estimation of the percentage of cells positive for intracellular cytokines and by the concentration of both cytokines secreted into the culture medium. Two models of mice exposure to ASM were used:1/ intraperitoneal injection (acute exposure), and 2/ oral exposure (subacute model). ASM exposure affected both IL-2 and IL-4 production and IL-2R α expression on activated lymphoid cells isolated from different lymphoid organs of both female and male mice. The effect was dependent on the route and duration of exposure, ASM dose and the age and sex of mice. A wide panel of changes is discussed. The prolonged exposure to ASM resulted in overproduction of IL-2 in both female and male mice and in overproduction of IL-4 in male mice. Acute exposure to ASM strongly affected IL-2 and IL-4 production, and the effect varied among lymphocytes from different lymphoid organs. Intracellular cytokines expression and the level of secreted cytokines seem to be good tools for the assessment of toxic effects of environmental pollution on the function of the immune system. [ABSTRACT FROM AUTHOR]