Intrauterine Growth Restriction: Cytokine Profiles of Trophoblast Antigen-Stimulated Maternal Lymphocytes

Intrauterine growth restriction (IUGR) is an important perinatal syndrome that poses several serious short- and long-term effects. We studied cytokine production by maternal peripheral blood lymphocytes stimulated by trophoblast antigens. 36 women with a diagnosis of IUGR and 22 healthy women with normal fetal growth were inducted. Peripheral blood mononuclear cells were stimulated with trophoblast antigens and levels of the proinflammatory cytokines IL-6, IL-8, IL-12, IL-23, IFNγ, and TNFα and the anti-inflammatory cytokines IL-4, IL-10, and IL-13 were measured in culture supernatants by ELISA. IL-8 was produced at higher levels by blood cells of the IUGR group than normal pregnant women, while IL-13 was produced at lower levels. IL-8, IFNγ, and TNFα were higher in IUGR with placental insufficiency than in normal pregnancy. IL-12 levels were higher and IL-10 levels were lower in IUGR with placental insufficiency than in IUGR without placental insufficiency. We suggest that a stronger pro-inflammatory bias exists in IUGR as compared to normal pregnancy and in IUGR with placental insufficiency when compared to IUGR without placental insufficiency. Several ratios of proinflammatory to anti-inflammatory cytokines also support the existence of an inflammatory bias in IUGR

Histological characterization of the Dicer1 mutant zebrafish retina

Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. DICER1, a multidomain RNase III endoribonuclease, plays a critical role in microRNA (miRNA) and RNA-interference (RNAi) functional pathways. Loss of Dicer1 affects different developmental processes. Dicer1 is essential for retinal development and maintenance. DICER1 was recently shown to have another function of silencing the toxicity of Alu RNAs in retinal pigment epithelium (RPE) cells, which are involved in the pathogenesis of age related macular degeneration. In this study, we characterized a Dicer1 mutant fish line, which carries a nonsense mutation (W1457Ter) induced by N-ethyl-N-nitrosourea mutagenesis. Zebrafish DICER1 protein is highly conserved in the evolution. Zebrafish Dicer1 is expressed at the earliest stages of zebrafish development and persists into late developmental stages; it is widely expressed in adult tissues. Homozygous Dicer1 mutant fish (DICER1W1457Ter/W1457Ter) have an arrest in early growth with significantly smaller eyes and are dead at 14–18 dpf. Heterozygous Dicer1mutant fish have similar retinal structure to that of control fish; the retinal pigment epithelium (RPE) cells are normal with no sign of degeneration at the age of 20 months. 1

Impaired immune function in Gulf War Illness

<p>Abstract</p> <p>Background</p> <p>Gulf War Illness (GWI) remains a serious health consequence for at least 11,000 veterans of the first Gulf War in the early 1990s. Our understanding of the health consequences that resulted remains inadequate, and this is of great concern with another deployment to the same theater of operations occurring now. Chronic immune cell dysfunction and activation have been demonstrated in patients with GWI, although the literature is not uniform. We exposed GWI patients and matched controls to an exercise challenge to explore differences in immune cell function measured by classic immune assays and gene expression profiling.</p> <p>Methods</p> <p>This pilot study enrolled 9 GWI cases identified from the Department of Veterans Affairs GWI registry, and 11 sedentary control veterans who had not been deployed to the Persian Gulf and were matched to cases by sex, body mass index (BMI) and age. We measured peripheral blood cell numbers, NK cytotoxicity, cytokines and expression levels of 20,000 genes immediately before, immediately after and 4 hours following a standard bicycle ergometer exercise challenge.</p> <p>Results</p> <p>A repeated-measures analysis of variance revealed statistically significant differences for three NK cell subsets and NK cytotoxicity between cases and controls (p < 0.05). Linear regression analysis correlating NK cell numbers to the gene expression profiles showed high correlation of genes associated with NK cell function, serving as a biologic validation of both the <it>in vitro </it>assays and the microarray platform. Intracellular perforin levels in NK and CD8 T-cells trended lower and showed a flatter profile in GWI cases than controls, as did the expression levels of the perforin gene PRF1. Genes distinguishing cases from controls were associated with the glucocorticoid signaling pathway.</p> <p>Conclusion</p> <p>GWI patients demonstrated impaired immune function as demonstrated by decreased NK cytotoxicity and altered gene expression associated with NK cell function. Pro-inflammatory cytokines, T-cell ratios, and dysregulated mediators of the stress response (including salivary cortisol) were also altered in GWI cases compared to control subjects. An interesting and potentially important observation was that the exercise challenge augments these differences, with the most significant effects observed immediately after the stressor, possibly implicating some block in the NK and CD8 T-cells ability to respond to "stress-mediated activation". This has positive implications for the development of laboratory diagnostic tests for this syndrome and provides a paradigm for exploration of the immuno-physiological mechanisms that are operating in GWI, and similar complex syndromes. Our results do not necessarily elucidate the cause of GWI, but they do reveal a role for immune cell dysfunction in sustaining illness.</p

Correlation of Proinflammatory and Anti-Inflammatory Cytokine Levels with Histopathological Changes in an Adult Mouse Lung Model of Campylobacter jejuni Infection▿

Campylobacter jejuni is a major cause of diarrhea in humans. A mouse lung model of infection was previously established for C. jejuni. We used this model to study cytokine production in the lungs and correlated it with pathological changes. C. jejuni strain 81-176 or sterile phosphate-buffered saline was intranasally inoculated into adult BALB/c mice. The levels of proinflammatory cytokines (gamma interferon, tumor necrosis factor alpha, interleukin-1β [IL-1β], IL-2) and anti-inflammatory cytokines (IL-4, IL-10), in addition to those of IL-6, were assessed on days 1, 3, and 5 postinfection by enzyme-linked immunosorbent assay, and the ratios of proinflammatory cytokines to anti-inflammatory cytokines were calculated. Since IL-6 is unique in that it is both a proinflammatory cytokine and a TH2 cytokine, it was considered to be both in the determination of these ratios. The significance of the cytokine levels and ratios were determined by the Mann-Whitney U test (P ≤ 0.05). The induction of proinflammatory cytokines in the lungs of infected mice, as indicated by the cytokine levels and ratios, coincided with the accumulation of neutrophils and activated macrophages, in addition to the clearance of the bacterial load and bacteriumlike structures that we have previously shown in the same groups of mice. This was followed by increased levels of anti-inflammatory cytokines and the resolution of inflammation and pathology in the lungs. This study demonstrates the dynamics of cytokine production and their correlation with tissue inflammation and the resolution of infection. This model is useful for further studies of the pathogenesis of C. jejuni infection and vaccine evaluation

Circulatory pattern of cytokines, adipokines and bone markers in postmenopausal women with low BMD

Fawaz Y Azizieh,1 Diaa Shehab,2 Khaled Al Jarallah,2 Olusegun Mojiminiyi,3 Renu Gupta,4 Raj Raghupathy51Department of Mathematics and Natural Sciences, International Centre for Applied Mathematics and Computational Bioengineering, Gulf University for Science and Technology, Kuwait City, Kuwait; 2Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait; 3Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait; 4Department of Radiology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait; 5Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait City, KuwaitObjective: In&nbsp;addition to some well-characterized bone turnover markers (BTMs), cytokines and adipokines have also been suggested to be linked to osteoporosis seen in menopause. However, there is much controversy on the possible association between these markers and bone mineral density (BMD). This study was aimed at measuring circulatory levels of selected cytokines, adipokines and BTMs in postmenopausal women with normal and low BMD.Methods: The study population included 71 post-menopausal women, of whom 25 had normal BMD, 31 had osteopenia and 13 had osteoporosis. Circulatory levels of selected pro-resorptive (TNF-&alpha;, IL-1&beta;, IL-6, IL-8, IL-12, IL-17), anti-resorptive (IFN-&gamma;, IL-4, IL-10, IL-13, TGF-&beta;) and five adipokine markers (adiponectin, adipsin, lipocalin-2/NGAL, PAI-1 and resistin) were measured using the Multiplex system and read on the Magpix ELISA platform. Further, two bone turnover markers (PINP, CTX) as well as estradiol levels were assayed from the same samples.Results: While circulatory levels of cytokines were comparable between groups, women with low BMD had statistically significantly higher median circulatory levels of adipokines as compared to those with normal BMD. Further, while levels of CTX were not different between the two groups; PINP, PINP/CTX ratio and estradiol levels were significantly lower in women with low BMD. Levels of adiponectin, PINP, PINP/CTX ratio and estradiol correlated significantly with BMD of the hip and spine.Conclusion: The associations between various markers and BMD are complex and multivariate. Our data provide insights into the possible use of circulatory levels of cytokines, adipokines and bone turnover markers on the pathogenesis of postmenopausal osteoporosis because of the well-documented effects of these molecules on bone tissue and their relevance to osteoporosis.Keywords: cytokines, adipokines, BTM, osteoporosis, menopaus