The female genital tract is a mucosal epithelium that has an array of factors contributing to the cervicovaginal immune environment. Like with systemic immunity, innate and adaptive immune mediators are integrated in the efficiency for fighting infections in the female genital tract. Our study addresses the role of pregnancy and HIV infection on concentrations of cytokines in genital tract fluid that play a role in HIV sexual transmission. We focused on two pathways: The NF-KB inflammation pathway that has been implicated in susceptibility to HIV infection, and two interferon pathways that have been associated with antiviral immune defense. We hypothesized that pregnant women have increased proinflammatory cytokines in genital secretions, potentially putting them at increased risk for HIV infection, and that HIV-infected women could have upregulated Type 1 interferon pathways that may regulate HIV replication in the genital tract, and infection by other viruses. This study compared the immune mediator profiles in genital secretions of women between the ages of 18 and 40 years old belonging to four groups: HIV Negative/ Non Pregnant, HIV Negative/Pregnant, HIV Positive/ Non Pregnant, and HIV positive/ pregnant. Cytokine concentrations in cervicovaginal lavage fluid were measured using ELISA and MAGPIX assays. A number of statistical methods were used to characterize cytokine pathways and to link pathway associated cytokines to HIV serostatus and/or pregnancy. The study showed that HIV positive women had higher levels of proinflammatory cytokines including IL-1α, IL-2RA, IL-4, IL-5, IL-6, IL-7, IL-12, IL-17, MIF, MIG, MIP-1ß, SCGF, TNF-α, and TRAIL. Only the antimicrobial peptide lysozyme was significantly decreased in HIV positive women. However, lysozyme was significantly increased in pregnant women where as the following cytokines were significantly decreased in pregnant women: ß-NGF, G-CSF, GM-CSF, GRO-α, HGF, IGN-α2, IFN-γ, IL-2RA, IL-3, IL-4, IL-6, IL-7, IL-12, IL-13, IL-16, IL-17, TNF-α, TRAIL. The correlation analysis showed that HIV positive nonpregnant women could have upregulated: NFκB, type I interferon and interferon-γ pathways. The correlation analysis showed that the NFκB pathway could be upregulated in pregnant HIV negative women and these findings suggest that vaginal inflammation may play a role in HIV transmission from HIV-infected women to uninfected pregnant women. Moreover, upregulated interferon pathways could help understand how the body regulates genital viral infections in HIV-infected women.

A hipóxia tecidual tem sido apontada como importante fator na patogênese da Doença Renal Crônica (DRC). No entanto, faltam evidências diretas de que a exposição prolongada à hipóxia tecidual inicie ou agrave a DRC. Nós testamos essa hipótese expondo cronicamente ratos normais e ratos com nefrectomia de 5/6 (Nx) à hipóxia. Além disso, investigamos se tal efeito da hipóxia envolveria a ativação da imunidade inata. Ratos Munich-Wistar machos adultos foram submetidos a Nx (n = 54) ou cirurgia simulada (Sham, n = 52). Vinte e seis ratos sham (S+nor) e 26 Nx (Nx+nor) permaneceram em normóxia, enquanto 26 ratos sham (S+hip) e 28 Nx (Nx+hip) foram mantidos em uma câmara de hipóxia normobárica (12% O2) por 8 semanas. Confirmamos a existência de hipóxia tecidual por imuno-histoquímica para Pimonidazol (Hypoxyprobe tm). A hipóxia foi confinada à área medular em S+nor e expandiu-se à área cortical em S+hip. A hipóxia não promoveu lesão renal nem elevação do conteúdo de IL-1beta ou TLR-4 em Sham. Em Nx, a hipóxia se estendeu para a área cortical, um processo que foi intensificado em Nx+hip, mas, inesperadamente, atenuou a hipertensão, a ativação da imunidade inata, a inflamação, a lesão renal e o estresse oxidativo. Em desacordo com os conceitos atuais, o presente estudo traz evidência de que a hipóxia pode exercer um efeito renoprotetor no modelo Nx, ao invés de atuar como um fator de lesão renal. Os mecanismos desse inesperado efeito benéfico não são claros, e podem envolver inibição da via do NF-kB, melhora do estresse oxidativo e limitação da produção de angiotensina II pelo tecido renal / Hypoxia is thought to influence the pathogenesis of chronic kidney disease (CKD), but direct evidence that prolonged exposure to tissue hypoxia initiates or aggravates CKD is lacking. We tested this hypothesis by chronically exposing normal rats and rats with 5/6 nephrectomy (Nx) to hypoxia. In addition, we investigated whether such effect of hypoxia would involve activation of innate immunity. Adult male Munich-Wistar rats underwent Nx (n=54) or sham surgery (sham, n=52). Twenty six sham (S+nor) and 26 Nx (Nx+nor) rats remained in normoxia, while 26 sham rats (S+hyp) and 28 Nx rats (Nx+hyp) were kept in a normobaric hypoxia chamber (12% O2) for 8 weeks. Hypoxia was confirmed by immunohistochemistry for Pimonidazole (Hypoxyprobe®). Hypoxia was confined to the medullar area in S+nor and spread to the cortical area in S+hyp. Exposure to hypoxia promoted no renal injury or elevation of the content of IL1beta or TLR-4 in Sham. In Nx, hypoxia extended to the cortical area, a process that was intensified in Nx+hyp but, unexpectedly, attenuated hypertension, inflammation, innate immunity activation, renal injury and oxidative stress. The present study, in disagreement with current concepts, shows evidence that hypoxia exerts a renoprotective effect in the Nx model, instead of acting as a factor of renal injury. The mechanisms for this unexpected beneficial effect are unclear, and may involve NF-kB inhibition, amelioration of oxidative stress and limitation of angiotensine II production by the renal tissue