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Biomedical subjects

L Stanciu

Publications and source records attributed to L Stanciu.

At least 19 recordsLinked to original sources
PubMed2003

The effects of Mycobacterium vaccae on allergen-induced airway responses in atopic asthma.

T-helper (Th)2 cytokines play a central role in asthma. Therefore, a double-blind randomised study was conducted to investigate whether heat-killed Mycobacterium vaccae (SRL172), a potent downregulator of Th2 cytokines, can reduce allergen-induced airway responses in patients with atopic asthma. A total 24 male asthmatics participated in this study. A bronchial allergen challenge was performed along with early (EAR) and late asthmatic responses (LAR) 2 weeks before and 3 weeks after a single intradermal injection of SRL172 or placebo. Before and after treatment, serum immunoglobulin (Ig)E levels and in vitro production of interleukin (IL)-5 by peripheral blood lymphocytes were studied. Neither treatment affected the EAR. SRL172 caused a mean 34% reduction of the area under the curve of the forced expiratory volume in one second (FEV1) changes during the LAR, which failed to reach conventional statistical significance when compared with placebo. SRL172 also caused a mean 25% decrease in the maximum fall in FEV1 during LAR, but this was not significantly different from placebo. SRL172 caused a reduction in serum IgE and IL-5 synthesis in vitro 3 weeks post-treatment (p = 0.07). This study shows a trend toward significance for the effects of heat-killed Mycobacterium vaccae (SRL172) on allergen-induced airway responses. Further clinical trials, involving multiple dosing, are needed.

Adult↗
PubMed1999

Essential role for both CD80 and CD86 costimulation, but not CD40 interactions, in allergen-induced Th2 cytokine production from asthmatic bronchial tissue: role for alphabeta, but not gammadelta, T cells.

CD80 and CD86 interact with CD28 and deliver costimulatory signals required for T cell activation. We demonstrate that ex vivo allergen stimulation of bronchial biopsy tissue from mild atopic asthmatic, but not atopic nonasthmatic, subjects induced production of IL-5, IL-4, and IL-13. Explants from both study groups did not produce IFN-gamma, but secreted the chemokine RANTES without any overt stimulation. In addition to allergen, stimulation of asthmatic explants with mAbs to CD3 and TCR-alphabeta but not TCR-gammadelta induced IL-5 secretion. Allergen-induced IL-5 and IL-13 production by the asthmatic tissue was inhibited by anti-CD80 and, to a lesser extent, by anti-CD86 mAbs. In contrast, the production of these cytokines by PBMCs was not affected by mAbs to CD80, was inhibited by anti-CD86, and was strongly attenuated in the presence of both Abs. FACS analysis revealed that stimulated asthmatic bronchial tissue was comprised of CD4+ T cells that expressed surface CD28 (75. 3%) but little CTLA-4 (4.0%). Neutralizing mAbs to CD40 ligand had no effect on the cytokine levels produced by asthmatic tissue or PBMCs. Collectively, these findings suggest that allergen-specific alphabeta T cells are resident in asthmatic bronchial tissue and demonstrate that costimulation by both CD80 and CD86 is essential for allergen-induced cytokine production. In contrast, CD86 appears to be the principal costimulatory molecule required in PBMC responses. Attenuation of type 2 alphabeta T cell responses in the bronchial mucosa by blocking these costimulatory molecules may be of therapeutic potential in asthma.

Adult↗
PubMed1997

Cell infiltration, ICAM-1 expression, and eosinophil chemotactic activity in asthmatic sputum.

We have applied the technique of sputum induction by hypertonic saline in asthmatics and nonatopic control subjects to study an array of indices of airway inflammation believed to be relevant to asthma pathogenesis. Compatible with a central role for eosinophils and mast cells in asthma, sputum of asthmatic subjects contained increased numbers of eosinophils and levels of eosinophil cationic protein (ECP) and mast cell tryptase. Eosinophil numbers, and ECP and histamine levels correlated with the degree of methacholine airways responsiveness, and ECP, tryptase, and histamine correlated with raised concentrations of albumin. Using the micro-Boyden chamber technique eosinophil chemotactic activity was identified only in the sputum from asthmatics. The correlation between the raised levels of total IgA, IL-8/IgA complexes, and tryptase and the degree of sputum eosinophilia and ECP levels, suggests possible mechanisms for eosinophil chemotaxis and activation in asthma. Row cytometric analysis of sputum lymphocytes showed an increase in CD4+ T cells and T cells expressing intercellular adhesion molecule-1 (ICAM-1) in asthma which, together with the finding of raised levels of soluble ICAM-1 in the sputum, indicates upregulation of this adhesion molecule. Finally, the proportion of CD16+ natural killer (NK) cells was reduced in the sputum of asthmatics. These observations highlight the importance of the airway inflammation in causing asthma and further confirm the usefulness of sputum induction as a tool in asthma research.

Adult↗
PubMed1995

Cyclic nucleotide phosphodiesterase isoenzyme activities in human alveolar macrophages.

BACKGROUND: Alveolar macrophages and their precursors, the monocytes are involved in airway inflammation in asthma. An increase in intracellular cAMP by PDE inhibitors is known to suppress macrophage and monocyte functions. A comparison of the PDE-isoenzyme profiles of human alveolar macrophages from normal and atopic donors and of human peripheral blood monocytes might form a basis to differentially affect functions of these cells by PDE inhibitors. OBJECTIVE: The study compares the PDE isoenzyme activity profiles of human alveolar macrophages from normal and atopic asthmatic donors and human peripheral blood monocytes. In addition, the effect of in vitro maturation of monocytes on their PDE isoenzyme profile is studied. METHODS: Macrophages were purified (95-97%) by adherence to plastic, and blood monocytes were purified (88%) by counter-current elutriation. PDE isoenzyme activity profiles were investigated using isoenzyme selective inhibitors and activators. RESULTS: In macrophages substantial PDE I activity, which was significantly higher than PDE III-V activity was detected and PDE II was absent. PDE III was membrane-bound whereas PDE I, IV and V were soluble. No difference was found between alveolar macrophages of normal donors and atopic asthmatics. Monocytes exclusively contained PDE IV but their in vitro maturation led to a PDE isoenzyme profile similar to that of alveolar macrophages. CONCLUSION: These results indicate that human monocytes and alveolar macrophages are distinct targets for the effects of selective PDE inhibitors while alveolar macrophages from normal and atopic individuals appear to be equally sensitive.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

T lymphocytes bearing histamine receptors in patients with digestive neoplasm.

The inverse relationship between allergic diseases, particularly bronchial asthma, and cancer has been much debated these past years. This inverse relationship may be due to different levels of blood and tissue histamine, and its effect on lymphocytes with H2 receptors. A clinical study was performed on circulating histamine-bearing T cells and on in vivo and in vitro immune response to PPD and histamine in patients with a newly diagnosed digestive neoplasm and in patients with allergic bronchial asthma. The mean percentage of T lymphocytes with histamine receptors was significantly decreased in patients with digestive neoplasm and with allergic bronchial asthma as compared to healthy controls.

Adolescent↗
PubMed1990

Immunomodulation by histamine.

Blood histamine proved to be important for the immune homeostasis. By its direct action or by means of H-2 receptors it end or prevents the excessive immune response. Recent studies revealed changes in cell mediated immunity in subjects with atopia, with increased histaminemia and their obvious protection against cancer. In patients with cancer, hypogammaglobulinemia, AIDS, the depression of the immune responses was partly accounted for by the decrease of blood histamine and by the change of the number of H-2 receptors. Hence the attempt to treat these diseases with H-2 antagonists associated or not with histamine.

Animals↗
PubMed1983

Experimental study of antibiotic-induced immunosuppression in mice. 1. Humoral and cell-mediated immune responsiveness related to in vivo antibiotic treatment.

By using CBA/J mice as responders, the immunodepressive effect of seven antibacterial chemotherapeutic agents was tested, i.e. penicillin (pen), streptomycin (str), erythromycin (erm), kanamycin (kan), tetracycline (tet), colistin (col) and chloramphenicol (chl). Lymphocytotoxicity power, as well as the ability of each drug to influence secondary humoral (against sheep red blood cells or diphtheria anatoxin) or cell-mediated (against PPD and Coxsackie A9 virus) immunity were searched. Erm, col and chl markedly depressed humoral and cell-mediated immune responsiveness in vitro after in vivo treatment with non-cytotoxical amounts. The Th lymphocyte supplementation of B reactive spleen cell population recovered the immune capacity in col and chl in vivo-treated groups, but not in erm-treated group.

Animals↗
PubMed1983

Experimental study of antibiotic-induced immunosuppression in mice. II. Th, Ts and NC cell involvement.

In penicillin(pen), streptomycin(str), kanamycin(kan) and tetracycline(tet)-treated CBA/J adult mice, no difference was noticed as concerned spleen T "helper" (Th) cell activity, as studied by means of response to PHA of X-irradiated/whole T fraction cell mixtures in vitro. On the contrary, in erythromycin(erm), colistin(col) and chloramphenicol(chl)-treated groups, Th cell activity was significantly decreased. On the other hand, spleen T "suppressor" (Ts) cell activity (assayed by response to PHA of mixtures containing pre-incubated with Concanavalin A and whole T cells, respectively) was augmented in samples arising from chl-treated group. These results are also supported by experiments testing Th or Ts soluble factors, induced in spleen T cells belonging to each antibiotic-treated group and purified by affinity chromatography (Concanavalin A-Sepharose 4B columns). Thus, it was confirmed both Th cell deficiency in erm, col or chl-groups, and Ts cell augmentation in chl-group. As regards spleen "natural cytotoxic" (NC) cell activity, as tested in a xenogeneic "target" cell substrate, a diminished cytotoxic capacity manifested chl-group-derived NC cells, possibly by richness in own "non-specific suppressor" (NSS) cells. NC cell samples in vitro supplemented with NSS cells arising from suckling mouse spleens and a lower cytotoxic activity, in a larger extent in chl-group-derived NC cells, as compared to other groups. The pre-incubation of control-group-NC cells with several antibiotic preparations in vitro was followed by decrease of the cytotoxic values in erm, col and chl-samples, suggesting a drug-induced NC receptor "masking", that prevented "target" cell recognition in mice--II. In the case of NSS addition in vitro, as strong inhibition of the cytotoximity occurred in chl-treated NC cells derived from the control group, that proves a possible chloramphenicol-induced immunodepression by potentiation of NSS inhibitory effect on NC cells. Based upon data from the present work, as well as from the previous work, the authors suggest a classification of several mechanisms by which the antibacterial antibiotics can act as immunosuppressive.

Animals↗