EFFECTS OF LOW-DOSE-GAMMA RAYS ON THE IMMUNE SYSTEM OF DIFFERENT ANIMAL MODELS OF DISEASE

We reviewed the beneficial or harmful effects of low-dose ionizing radiation on several diseases based on a search of the literature. The attenuation of autoimmune manifestations in animal disease models irradiated with low-dose γ-rays was previously reported by several research groups, whereas the exacerbation of allergic manifestations was described by others. Based on a detailed examination of the literature, we divided animal disease models into two groups: one group consisting of collagen-induced arthritis (CIA), experimental encephalomyelitis (EAE), and systemic lupus erythematosus, the pathologies of which were attenuated by low-dose irradiation, and another group consisting of atopic dermatitis, asthma, and Hashimoto’s thyroiditis, the pathologies of which were exacerbated by low-dose irradiation. The same biological indicators, such as cytokine levels and Tcell subpopulations, were examined in these studies. Low-dose irradiation reduced interferon (IFN)-gamma (γ) and interleukin (IL)-6 levels and increased IL-5 levels and the percentage of CD4+CD25+Foxp3+Treg cells in almost all immunological disease cases examined. Variations in these biological indicators were attributed to the attenuation or exacerbation of the disease’s manifestation. We concluded that autoimmune diseases caused by autoantibodies were attenuated by low-dose irradiation, whereas diseases caused by antibodies against external antigens, such as atopic dermatitis, were exacerbated

The development of novel LTA4H modulators to selectively target LTB4 generation

The pro-inflammatory mediator leukotriene B4 (LTB4) is implicated in the pathologies of an array of diseases and thus represents an attractive therapeutic target. The enzyme leukotriene A4 hydrolase (LTA4H) catalyses the distal step in LTB4 synthesis and hence inhibitors of this enzyme have been actively pursued. Despite potent LTA4H inhibitors entering clinical trials all have failed to show efficacy. We recently identified a secondary anti-inflammatory role for LTA4H in degrading the neutrophil chemoattractant Pro-Gly-Pro (PGP) and rationalized that the failure of conventional LTA4H inhibitors may be that they inadvertently prevented PGP degradation. We demonstrate that these inhibitors do indeed fail to discriminate between the dual activities of LTA4H, and enable PGP accumulation in mice. Accordingly, we have developed novel compounds that potently inhibit LTB4 generation whilst leaving PGP degradation unperturbed. These novel compounds could represent a safer and superior class of LTA4H inhibitors for translation into the clinic

Evolutionarily Conserved Protein Sequences of Influenza A Viruses, Avian and Human, as Vaccine Targets

10.1371/journal.pone.0001190PLoS ONE21

Influenza virus-specific cytotoxic T cells in man; induction and properties of the cytotoxic cell.

Human peripheral blood lymphocytes have been sensitized in vitro to influenza virus antigen. After an induction period of 4--14 days, cytotoxic cells which lyse autologous influenza virus-infected lymphoid cells could be demonstrated. The cytotoxic cell is a T lymphocyte which shows specificity for sensitizing influenza virus type A or B. It cannot distinguish between major subtypes of influenza A virus. The use of virus-infected normal lymphoid cells as target cells overcame the difficulties of nonspecific killing encountered with some transformed cells