Glutathione Depletion Is Linked with Th2 Polarization in Mice with a Retrovirus-Induced Immunodeficiency Syndrome, Murine AIDS: Role of Proglutathione Molecules as Immunotherapeutics

Injection of the LP-BM5 murine leukemia virus into mice causes murine AIDS, a disease characterized by many dysfunctions of immunocompetent cells. To establish whether the disease is characterized by glutathione imbalance, reduced glutathione (GSH) and cysteine were quantified in different organs. A marked redox imbalance, consisting of GSH and/or cysteine depletion, was found in the lymphoid organs, such as the spleen and lymph nodes. Moreover, a significant decrease in cysteine and GSH levels in the pancreas and brain, respectively, was measured at 5 weeks postinfection. The Th2 immune response was predominant at all times investigated, as revealed by the expression of Th1/Th2 cytokines. Furthermore, investigation of the activation status of peritoneal macrophages showed that the expression of genetic markers of alternative activation, namely, Fizz1, Ym1, and Arginase1, was induced. Conversely, expression of inducible nitric oxide synthase, a marker of classical activation of macrophages, was detected only when Th1 cytokines were expressed at high levels. In vitro studies revealed that during the very early phases of infection, GSH depletion and the downregulation of interleukin-12 (IL-12) p40 mRNA were correlated with the dose of LP-BM5 used to infect the macrophages. Treatment of LP-BM5-infected mice with N-(N-acetyl-L-cysteinyl)-S-acetylcysteamine (I-152), an N-acetyl-cysteine supplier, restored GSH/cysteine levels in the organs, reduced the expression of alternatively activated macrophage markers, and increased the level of gamma interferon production, while it decreased the levels of Th2 cytokines, such as IL-4 and IL-5. Our findings thus establish a link between GSH deficiency and Th1/Th2 disequilibrium in LP-BM5 infection and indicate that I-152 can be used to restore the GSH level and a balanced Th1/Th2 response in infected mice

The immunosuppressive activity of Ascaris suum is due to high molecular weight components

The role of isolated components obtained by gel filtration chromatography of Ascaris suum body extract (Asc) on the modulation of the immune response to ovalbumin (OvA) was evaluated and correlated with the immunogenic properties of such components. We showed that high (PI), but not low (PIII), molecular weight components have the ability to inhibit OvA-induced immediate and DTH reactions, lymph node (LN) cell proliferation, cytokine (IL-2, interferon-gamma (IFN-γ), IL-4 and IL-10) and antibody (IgG1, IgG2a, IgM and IgE) production in mice concomitantly immunized with OvA and these high mol. wt components. The pattern of cytokines synthesized in response to PI or PIII was totally different: the former induced more IL-4 and IL-10 and the latter more IL-2 and IFN-γ. The levels of Asc-specific IgG1 antibodies were higher in mice immunized with OvA plus PI and IgG2a anti-Asc antibodies predominated in those immunized with PIII. IgE antibody production, however, was low in the former group of mice. These results indicate that the high mol. wt components present in the body extract from the helminth A. suum are responsible for its suppressive effect upon Th1- and Th2-dependent immune responses to an unrelated antigen. The suppression of the Th1-dependent parameters could be related to high-level expression of IL-4 and IL-10 induced by such components

The Impact of Financial Hardship on Single Parents: An Exploration of the Journey From Social Distress to Seeking Help

Single parent families are at high risk of financial hardship which may impact on psychological wellbeing. This study explored the impact of financial hardship on wellbeing on 15 single parents. Semi-structured interviews were conducted and analysed using constructivist thematic analysis. Participants described food and fuel poverty, and the need to make sacrifices to ensure that children's basic needs were met. In some cases, participants went without food and struggled to pay bills. Isolation, anxiety, depression, paranoia, and suicidal thoughts were described. However, participants reported that psychological services not able to take the needs of single parents in to account. Support for single parents must acknowledge the impact of social circumstances and give more consideration economic drivers of distress.</p