Prostaglandin E1 attenuates impairment of cellular immunity after cardiopulmonary bypass.

OBJECTIVE: It is well documented that cardiopulmonary bypass (CPB) severely impairs cellular immunity. The objective of this study was to investigate the effect of prostaglandin E1 (PGE1) on cellular immunity after CPB. METHODS: Patients who underwent elective cardiac surgery were randomly divided into the PGE1 group (n=12) and the control group (n=12). In the PGE1 group, PGE1 was administered at 20 ng/kg/min from just after the induction of anesthesia to the end of surgery. Peripheral blood mononuclear cells (PBMCs) were taken before anesthesia and on postoperative days 1, 3 and 7 (POD 1, POD 3 and POD 7). Proliferation responses of T cells to phytohemagglutinin (PHA) and pure protein derivative (PPD) antigen were measured as indicators of cellular immunity. RESULTS: PGE1 significantly attenuated the impairment of both PHA and PPD response after cardiac surgery on POD 1 (PHA response, 30 +/- 21% vs. 53 +/- 32%, control vs. PGE, p=0.048; PPD response, 18 +/- 21% vs. 39 +/- 27%, control vs. PGE, p=0.046). The reduced glutathione content of PBMCs in the control group was significantly decreased on POD 1. CONCLUSION: PGE1 attenuated the impairment of cellular immunity after cardiac surgery with CPB by reducing oxidative stress on PBMCs.

Effects of breast milk from allergic and non-allergic mothers on mitogen- and allergen-induced cytokine production.

Breast milk contains several components that provide specific immunity and affect the maturation of the infant's immune system. The aim of this study was to analyze the effects of breast milk, on mitogen- and allergen-induced cytokine production from cord blood mononuclear cells (CBMC), and if those effects differ between allergic and non-allergic mothers. The cells were incubated for 96 h with phytohemagglutinin (PHA), ovalbumin or cat dander in the presence of various dilutions of colostrum. Colostrum inhibited both mitogen- and cat-induced IFN-gamma and mitogen-induced interleukin-4 (IL-4) production. The inhibition on IFN-gamma production was to some extent caused by TGF-beta, as the effect was modified when an anti-TGF-beta antibody was added to the cultures. In contrast, colostrum enhanced allergen-induced production of the Th2-like cytokines IL-5 and IL-13, and this was accompanied with increased production of IL-10. No differences were found between allergic and non-allergic mothers. The inhibitory effect of breast milk on IFN-gamma production, which was partly due to the high levels of TGF-beta, together with the enhancing effect on IL-10 secretion, confirm that breast milk is anti-inflammatory. Although the production of IL-5 and IL-13 was enhanced by colostrum, this was accompanied with an increased production of IL-10. Together with the high levels of TGF-beta in breast milk and inhibitory effect of colostrum on IL-4 production, this suggests a possible mechanism whereby breast-feeding may protect against the development of allergy. Despite differences in the composition of breast milk between allergic and non-allergic mothers, the effects of breast milk on cytokine production from CBMC were independent of the atopic status of the mothers.

Effects of in ovo and acute diazepam treatments on peripheral benzodiazepine receptors and cutaneous basophil hypersensitivity in chickens.

Prenatal diazepam treatment impairs immune responses in mammals, but chicken embryos allow experimental manipulation isolated from maternal influences on embryo development. In ovodiazepam treatment in chickens decreased macrophage spreading and phagocytosis. In the present experiment, we investigated the effects of in ovoand/or acute diazepam treatments on phytohemagglutinin (PHA)-induced cutaneous basophil hypersensitivity (CBH) response in chickens. Forty day-old chickens, treated in ovo with 8 mg diazepam/kg, 2 ml diazepam vehicle/kg, or sham-manipulated. were subsequently treated po with 2 mg diazepam/kg or with diazepam's vehicle 1 h before PHA injection. The existence of an interaction between diazepam treatments was shown. Birds acutely treated with diazepam exhibited an increment in CBH response. In contrast, in ovo diazepam treatment per se did no change animals' response to PHA, but antagonized acute diazepam effects on CBH response. The results occurred through direct and/or indirect action of diazepam on cytokine and/or glucocorticoid hormone production and release. In the former case, the effects might be related to stimulation of peripheral benzodiazepine receptors (PBR) on immune cells, thus changing the cytokine cascade, while in the latter instance they might be mediated through glucocorticoid hormones via PBR stimulation in the adrenal gland cells.

Screening and fractionation of plant extracts with antiproliferative activity on human peripheral blood mononuclear cells.

Three hundred and thirteen extracts from 136 Brazilian plant species belonging to 36 families were tested for their suppressive activity on phytohemaglutinin (PHA) stimulated proliferation of human peripheral blood mononuclear cells (PBMC). The proliferation was evaluated by the amount of [3H]-thymidine incorporated by the cells. Twenty extracts inhibited or strongly reduced the proliferation in a dose-dependent manner at doses between 10 and 100 micro g/ml. Three of these extracts appeared to be non-toxic to lymphocytes, according to the trypan blue permeability assay and visual inspection using optical microscopy. Bioassay-guided fractionation of Alomia myriadenia extract showed that myriadenolide, a labdane diterpene known to occur in this species, could account for the observed activity of the crude extract. Using a similar protocol, an active fraction of the extract from Gaylussacia brasiliensis was obtained. Analysis of the 1H and 13C NMR spectra of this fraction indicates the presence of an acetylated triterpene whose characterization is underway. The extract of Himatanthus obovatus is currently under investigation.

Interleukin-13 secretion by normal and posttransplant T lymphocytes; in vitro studies of cellular immune responses in the presence of acute leukaemia blast cells.

T lymphocyte secretion of interleukin-13 (IL-13) in response to different activation signals was characterized in vitro. IL-13 release was investigated when virus transformed B lymphocytes or acute myelogenous leukaemia (AML) blasts were used as accessory cells during T cell activation. First, a majority of both CD4+ and CD8+ TCR alpha beta + T lymphocyte clones, derived from normal individuals and bone marrow transplant recipients, secreted IL-13 in response to a standardized mitogenic activation signal (phytohaemagglutinin + IL-2 + B lymphocyte accessory cells). The CD4+ cells showed significantly higher IL-13 levels than the CD8+ subsets. Second, when leukaemic accessory cells (more than 95% AML blasts) were used during T cell activation, IL-13 was released both during alloactivation of normal T lymphocytes and during mitogen activation of posttransplant T cells. Third, when normal T lymphocytes were stimulated with allogeneic AML blasts, addition of IL-13-neutralizing monoclonal antibodies decreased interferon gamma levels. Although addition of IL-13-neutralizing antibodies did not alter granulocyte-colony-stimulating factor secretion by allostimulating AML blasts, altered blast proliferation was detected for certain patients. Thus, most T cell clones can release IL-13, and IL-13 can modulate cytokine responses during T cell recognition of allogeneic AML cells.