[Reactive metabolites of oxygen, lipid peroxidation, total antioxidant capacity and vitamin E in essential arterial hypertension]. / Metaboliti reattivi dell'ossigeno, perossidazione lipidica, capacità antiossidante totale e vitamina E nell'ipertensione arteriosa essenziale.

Free radical oxidative stress has been implicated in the pathogenesis of a variety of human diseases. The purpose of this study was to explore the degree of oxidative stress in essential arterial hypertension (EAH). The study groups consisted of fifteen untreated EAH patients (WHO stages 1 and 2), aged 40 to 70 years, and fifteen, age and sex matched, normal controls. The levels of typical peroxidation products such as malondialdehyde and 4-hydroxyalkenals (with the LPO-586 test, Bioxytech), free radicals and other reactive oxygen metabolites (ROMs) (with the d-ROMs test, Diacron), vitamin E (with HPLC method) and total antioxidant capacity (with the TAS test, Randox) were determined in the plasma af all subjects. Compared to the control group EAH patients exhibited significantly higher ROMs levels (334.7 +/- 21.6 vs 249.2 +/- 23.3 Units, means values +/- S.E.M.), and of lipid peroxidation products (10.7 +/- 0.7 vs 8.09 +/- 0.9 nmol/ml). It must be noted that such increases were not observed in all EAH patients, but above all in those less young or with more severe hypertension. On the other hand no significant difference was found between EAH patients and normal controls as regards vitamin E concentration and total antioxidant capacity. These results suggest that EAH patients, in spite of their normal antioxidant defences, are more prone than normotensive subjects to oxidative stress because of an increased ROMs production. This could result in an inactivation of prostacyclin and NO, hence an enhancement of peripheral vascular resistance and an increase of hypertension. Another consequence might be an increased lipid peroxidation of low density lipoproteins, a condition which is known to be associated with accelerated atherosclerosis. The study of oxidant and antioxidant factors seems therefore useful in EAH patients in order to evaluate oxidative stress and to correct, if possible, the observed abnormalities with dietetic or pharmacologic therapy.

Role for CD30 in HIV expression.

CD30 is a member of the tumor necrosis factor (TNF)-receptor superfamily, whose ligand (CD30L) has been identified on B cells, activated macrophages and a subset of activated T cells. We show here that infection in vitro with human immunodeficiency virus (HIV) of CD4+ T-cell clones generated from HIV-seronegative individuals can enhance the expression of CD30, which often preceeds and is associated with the death of clonal T cells. Furthermore, cross-linking CD30 with an agonistic CD30-specific monoclonal antibody potentiated HIV replication induced by an insolubilized anti-CD3 antibody in T-cell lines generated from HIV-infected individuals. More importantly, paraformaldehyde-fixed CD8+ T-cell clones expressing CD30L enhanced HIV replication in anti-CD3-stimulated allogeneic or autologous HIV-infected CD4+ T-cell lines and such a potentiating effect was inhibited by an anti-CD30L antibody. The anti-CD30L antibody also exerted a suppressive effect on the spontaneous HIV replication occurring in lymph node cells, freshly derived from an HIV-seropositive patient showing CD30 expression in B cells and in a proportion of CD8+ T lymphocytes. Thus, CD30 triggering may play an important role in both HIV replication and the death of HIV-infected CD4+ T cells.

Expression and release of LAG-3-encoded protein by human CD4+ T cells are associated with IFN-gamma production .

The lymphocyte activation gene (LAG) -3 is a member of the immunoglobulin super-family that is selectively transcribed in human activated T and NK cells. In this work, the possibility that LAG-3 expression by human CD4+ T cells was preferentially related to one or another phenotype of cytokine secretion was investigated. Surface LAG-3 expression correlated with IFN-gamma, but not IL-4, production in antigen-stimulated T cells and it was up-regulated by IL-12. Most activated CD4+ T cell clones with established Th1 or Th0 profiles of cytokine secretion expressed LAG-3 on their surface, whereas the great majority of Th2 clones showed neither surface LAG-3 nor LAG-3 mRNA expression. After activation, the majority of CD4+ T cell clones also released soluble LAG-3-related peptides, and such a release correlated positively with the production of IFN-gamma and inversely with the production of IL-4. Thus, LAG-3 expression by activated CD4+ human T cells appear to be preferentially associated with the differentiation/activation pathway leading to the production of IFN-gamma.

Polyinosinic acid: polycytidylic acid promotes T helper type 1-specific immune responses by stimulating macrophage production of interferon-alpha and interleukin-12.

The effects exerted on the development in vitro of Dermatophagoides pteronyssinus group I (Der p I)-specific T cell lines and T cell clones by addition of polyinosinic acid: polycytidylic acid (poly I:C) in lymphocyte bulk culture were examined. Der p I-specific T cell lines generated in presence of poly I:C exhibited reduced ability to produce interleukin (IL)-4 and IL-5 and developed into Der p I-specific CD4+ T cell clones showing a T helper (Th) type 0 or Th1, instead of Th0/Th2 cytokine profile. This effect was prevented by addition to lymphocyte bulk cultures of a mixture of antibodies specific for interferon (IFN)-alpha and IL-12, whereas the addition of anti-IFN-alpha or anti-IL-12 antibody alone was uneffective. Poly I:C also showed the ability to stimulate the production of noticeable amounts of both IFN-alpha and IL-12 by human monocytes. Taken together, these data suggest that poly I:C is a Th1-inducing agent whose activity is mediated by its ability to stimulate the production of IFN-alpha and IL-12 by monocytes.