Do indoor chemicals promote development of airway allergy?

UNLABELLED: Allergic asthma has increased worldwide in the industrialized countries. This review evaluates whether the major groups of indoor chemical exposures possess allergy-promoting (adjuvant) effects; formaldehyde was excluded, because of the size of the literature. Volatile organic compounds (VOCs) are used as an example of gases and vapors. The precipitation of asthmatic symptoms by VOC exposures is probably because of VOC levels considerably above typical indoor levels, or VOCs may be a surrogate for exposure to allergens, combustion products or dampness. Indoor particles possessed adjuvant effects in animal studies and allergy-promoting effects in humans. Quaternary ammonium compounds may possess adjuvant effects in animal studies and promoted sensitization in humans in occupational settings. The use of cleaning agents, anionic and non-ionic surfactants are not considered to possess an important adjuvant effect in the general population. Regarding phthalate exposures, results from animal and epidemiological studies were found to be discordant. There is little evidence that the indoor chemicals evaluated possess important adjuvant effects. If buildings are kept clean, dry and free of combustion products, the important question may be would it be profitable to look for lifestyle factors and non-chemical indoor exposures in order to abate airway allergy? PRACTICAL IMPLICATIONS: Indoor chemicals (pollutants) have been accused to promote development of airway allergy by adjuvant effects. In this review, we evaluated the scientific literature and found little support for the supposition that indoor chemicals possess important adjuvant effects. This rises the question: would it be profitable for abatement of airway allergy to look for non-chemical indoor exposures, including lifestyle factors, and exposures to allergens, microorganisms, including vira, and their interactions?

Are basophil histamine release and high affinity IgE receptor expression involved in asymptomatic skin sensitization?

BACKGROUND: Immunoglobulin (Ig)E-sensitized persons with positive skin prick test, but no allergy symptoms, are classified as being asymptomatic skin sensitized (AS). The allergic type 1 disease is dependant on IgE binding to the high affinity IgE-receptor (FcepsilonRI) expressed on basophils and mast cells. However, a relationship between the AS status and FcepsilonRI has not been investigated. We aimed to characterize basophils from AS by looking at histamine release (HR) (sensitivity and reactivity) and the FcepsilonRI molecule, and compare it with nonatopic (NA) or allergic (A) persons. METHODS: Blood was obtained from NA (n = 14), grass and/or birch A persons (n = 17) and mono-sensitized grass or birch pollen AS (n = 12). The basophil sensitivity and reactivity were examined by anti-IgE triggered HR. Surface expression of FcepsilonRI and IgE were measured by flow cytometry, FcepsilonRIalpha protein was identified using a radioimmunoassay and Western blot. mRNA coding for the classic FcepsilonRIbeta-chain and the truncated form (FcepsilonRIbetaT) were determined by real-time PCR. RESULTS: The AS group was less reactive than NA or A persons when triggered by anti-IgE and had a significant higher number of nonresponders. However, there was no difference in sensitivity among the three groups and furthermore; the groups did not vary in FcepsilonRI- and IgE-surface expression, FcepsilonRIalpha-protein level or beta/betaT ratio. CONCLUSION: Basophils from AS persons are less reactive and include more nonresponders than basophils from NA and A persons, but do not differ regarding the FcepsilonRI molecule.

LPS-induced cytokine production in the monocytic cell line THP-1 determined by multiple quantitative competitive PCR (QC-PCR).

BACKGROUND: Quantifying cytokines on the protein level can be problematic because of low concentrations or degradation during sample handling. Aiming towards finding a simple method by which to quantify cytokines on the mRNA level, we combined existing and established molecular biology techniques. Based on the principle of quantitative competitive RT-PCR with a DNA-competitor, IL-1beta, IL-6, IL-12alpha and the housekeeping enzyme GAPDH are measured at levels down to 200 copies of mRNA. METHODS: As a source of mRNA, the total RNA from 4 samples of 5 x 10(6) THP-1 cells stimulated with LPS (1 microg/ml for 24 h) was isolated. For competitors, we constructed sequences similar to the target sequences, but with deletion or insertion of 10-15% of the target length. For validating this method, we performed first strand synthesis on different days using different amounts of RNA (1-4 microg) isolated from the same pool of cells. Quantitative competitive PCR was accomplished using different amounts of cDNA (0.125-4 microL). Using IL-1beta as an example, the assay was validated for a dynamic range of 5-300 x 10(3) copies. RESULTS: A linear correlation was found between output and amount of RNA for cDNA synthesis, signifying that the final result of the analysis was linearly related to the amount of RNA or cDNA when operating within the range 1-4 microg (RNA isolation). CONCLUSION: The quantitative, competitive RT-PCR produces highly reproducible results within a 60-fold dynamic range.

In vitro effects of monophthalates on cytokine expression in the monocytic cell line THP-1 and in peripheral blood mononuclear cells from allergic and non-allergic donors.

It has recently been shown that plasticizers are present in indoor air dust, which may lead to human exposure via the inhalation route. Moreover, studies have indicated that plasticizers may possess adjuvant effects increasing the health damaging potential of allergens. The aim of this study was to investigate the in vitro effect of metabolites of phthalate plastisizers, such as whether an adjuvant effect is paralleled by changes of the cytokine expression in the monocytic cell line THP-1 and in peripheral blood mononuclear cells (PBMCs) from allergics and non-allergics. The toxicity monitored by cell viability was determined by incubating THP-1 cells with a 10-fold dilution series of monophthalates for 24 h. At different points in time cytokine expression (IL-1beta, IL-6, IL-12alpha (p35)) in THP-1 cells incubated with non-toxic concentrations of monophthalate (2-20 microg/ml)+/-LPS (1 microg/ml) were determined using Quantitative Competitive RT-PCR. PBMCs from allergics and non-allergics were incubated with monophthalate 220 microg/ml) for up to 48 h and cytokine expression (IL-4, IL-5, IFN-gamma) was measured using real-time PCR. The cytotoxic level of monophthalates is 20-200 microg/ml, depending on the individual monophthalate. There seems to be a correlation between increasing side-chain length and toxicity. Monophthalates did not induce changes in cytokine expression in THP-1 cells, though there is an increase when co-incubating with LPS. Cytokine expression in PBMC seems virtually unchanged when co-incubated with monophthalate, though mono-n-butyl phthalate (MBUP) tends to increase the level of IL-4 in PBMCs from allergic individuals. The two cellular models demonstrated the dynamics of regulated cytokine mRNA and are applicable for in vitro immunotoxicological investigations. The results regarding monophthalates suggest these to have a limited effect on cytokine expression in the monocytic cell line THP-1 and weak effect on cytokine expression in PBMCs from allergic and non-allergic individuals.

CXCR3 expression on CD34(+) hemopoietic progenitors induced by granulocyte-macrophage colony-stimulating factor: II. Signaling pathways involved.

CXCR3, known to have four ligands (IFN-gamma inducible protein 10 (gamma IP-10), monokine induced by IFN-gamma (Mig), I-TAC, and 6Ckine), is predominantly expressed on memory/activated T lymphocytes. We recently reported that GM-CSF induces CXCR3 expression on CD34(+) hemopoietic progenitors, in which gamma IP-10 and Mig induce chemotaxis and adhesion. Here we further report that stimulation with GM-CSF causes phosphorylation of Syk protein kinase, but neither Casitas B-lineage lymphoma (Cbl) nor Cbl-b in CD34(+) hemopoietic progenitors can be blocked by anti-CD116 mAb. Specific Syk blocking generated by PNA antisense completely inhibits GM-CSF-induced CXCR3 expression in CD34(+) progenitors at both mRNA and protein as well as at functional levels (chemotaxis and adhesion). Cbl and Cbl-b blocking have no such effects. Thus, GM-CSF binds to its receptor CD116, and consequently activates Syk phosphorylation, which leads to induce CXCR3 expression. gamma IP-10 and Mig can induce Syk, Cbl, and Cbl-b phosphorylation in CD34(+) progenitors by means of CXCR3. gamma IP-10 or Mig has induced neither chemotaxis nor adhesion in GM-CSF-stimulated Cbl-b-blocked CD34(+) hemopoietic progenitors, whereas SDF-1alpha induces both chemotaxis and adhesion in these cells. Interestingly, gamma IP-10 and Mig can induce chemotaxis and adhesion in GM-CSF-stimulated Syk- or Cbl-blocked CD34(+) hemopoietic progenitors. Thus, Cbl-b, but not Syk and Cbl phosphorylation, is essential for gamma IP-10- and Mig-induced chemotaxis and adhesion in CD34(+) hemopoietic progenitors. This study provides a useful insight into novel signaling transduction pathways of the functions of CXCR3/gamma IP-10 and Mig, which may be especially important in the cytokine/chemokine environment for mobilization, homing, and recruitment during proliferation, differentiation, and maturation of hemopoietic progenitor cells.

Detergents in the indoor environment - what is the evidence for an allergy promoting effect? Known and postulated mechanisms.

IgE-mediated allergic diseases, such as asthma and rhinitis seem to be increasing in industrialised societies. One possible explanation for this could be the increased use of more effective and aggressive detergents. The surfactants from these could interfere with the sensitisation process in which specific IgE is formed to ubiquitously occurring environmental allergens. Only sparse data exist in relation to surfactants and allergic sensitization. However, it can be speculated that the strong surfactant properties of some of ingredients used in modem detergents may interfere with some of the intricate cellular interactions taking place along the immunological pathways. These include formation of IL-4 and IL-5 producing T helper lymphocytes type 2 and the B-lymphocyte isotype switch, which leads to production of specific IgE. Candidates for experimental studies of such phenomena on the cellular level are proposed.

CXC chemokine receptor 4 expression and stromal cell-derived factor-1alpha-induced chemotaxis in CD4+ T lymphocytes are regulated by interleukin-4 and interleukin-10.

We report that interleukin (IL)-4 and IL-10 can significantly up- or down-regulate CXC chemokine receptor 4 (CXCR4) expression on CD4+ T lymphocytes, respectively. Stromal cell-derived factor-1alpha (SDF-1alpha)-induced CD4+ T-lymphocyte chemotaxis was also correspondingly regulated by IL-4 and IL-10. IL-4 and IL-10 up- or down-regulated CXCR4 mRNA expression in CD4+ T lymphocytes, respectively, as detected by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Scatchard analysis revealed a type of CXCR4 with affinity (Kd approximately 6.3 nM), and approximately 70,000 SDF-1alpha-binding sites per cell, among freshly isolated CD4+ T lymphocytes, and two types of CXCR4 with different affinities (Kd1 approximately 4.4 nM and Kd2 approximately 14.6 nM), and a total of approximately 130,000 SDF-1alpha-binding sites per cell, among IL-4-stimulated CD4+ T lymphocytes. The regulation of CXCR4 expression in CD4+ T lymphocytes by IL-4 and IL-10 could be blocked by a selective inhibitor of protein kinase (staurosporine) or by a selective inhibitor of cAMP- and cGMP-dependent protein kinase (H-8), indicating that these cytokines regulate CXCR4 on CD4+ T lymphocytes via both cAMP and cGMP signalling pathways. The fact that cyclosporin A or ionomycin were able to independently change the CXCR4 expression and block the effects of IL-4 and IL-10 on CXCR4 expression implied that the capacity of IL-4 and IL-10 to regulate CXCR4 on CD4+ T lymphocytes is not linked to calcium-mobilization stimulation. These results indicate that the effects of IL-4 and IL-10 on the CXCR4-SDF-1 receptor-ligand pair may be of particular importance in the cytokine/chemokine environment concerning the inflammatory processes and in the progression of human immunodeficiency virus (HIV) infection.