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

Assessment of whole-sediment chronic toxicity using sub-lethal endpoints with Monocorophium insidiosum

A whole-sediment test with the infaunal amphipod Monocorophium insidiosum has been developed to assess the long-term effects exerted by sediment contamination on survival, growth rates and attainment of sexual maturity. Juvenile amphipods were exposed for 28 days to a control sediment (native sediment) and three sediment samples collected in sites of the Venice Lagoon, characterized by contamination levels ranging from low to moderate, and absence of acute toxicity toward amphipods. Growth rate was estimated as daily length (μm d−1) and weight increments (μg d−1). The long-term exposure to the test sediments affected significantly both growth rate and attainment of sexual maturity of the females of M. insidiosum. In contrast, survival was high and uniform among all the samples, despite the contamination gradient. The results suggest growth to be the more reliable and statistically relevant endpoint. Attainment of sexual maturity, although allowed the identification of detrimental effects, was affected by a higher among-replicates variance as compared with growth rates, and thus less reliable than growth for the identification of impairments. The significant impairments observed both on growth and attainment of maturity evidenced the need to address the monitoring, also in the Lagoon of Venice, towards the assessment of the long-term effects on benthic species