scholarly journals Spaceflight and development of immune responses

1998 ◽  
Vol 85 (4) ◽  
pp. 1429-1433 ◽  
Author(s):  
Gerald Sonnenfeld ◽  
Mareva Foster ◽  
Darla Morton ◽  
Frederique Bailliard ◽  
Nina A. Fowler ◽  
...  
Keyword(s):  
Immune Responses ◽  
Bone Marrow Cells ◽  
Space Shuttle ◽  
Interferon Γ ◽  
Total Serum ◽  
Spleen Cells ◽  
Immunological Parameters ◽  
Pregnant Rats ◽  
Immune Parameters ◽  
Stimulating Factor

The NIH.R1 Space Shuttle experiment was designed to study the effects of spaceflight on rodent development. Pregnant rats were flown on the Space Shuttle for 11 days, and pregnant control rats were maintained in animal enclosure modules in a ground-based chamber under conditions approximating those in flight. Additional controls were in standard housing. The effects of the flight on immunological parameters of dams, fetuses, and pups were determined. Blastogenesis of spleen cells in response to mitogen was inhibited in flown dams but was not inhibited in cells from their pups. Interferon-γ production by spleen cells showed a trend toward inhibition in flown dams but not in their pups. The response of bone marrow cells to colony-stimulating factor showed a trend toward inhibition after spaceflight in dams, but the response of fetus and pup liver cells was not inhibited. Total serum IgG was not affected by spaceflight. None of the examined immune parameters that were altered in rat dams after spaceflight was found to be altered in their offspring.

Effects of spaceflight and PEG-IL-2 on rat physiological and immunological responses

1999 ◽  
Vol 86 (6) ◽  
pp. 2065-2076 ◽  
Author(s):  
Stephen K. Chapes ◽  
Steven J. Simske ◽  
Gerald Sonnenfeld ◽  
Edwin S. Miller ◽  
Robert J. Zimmerman
Keyword(s):  
Peritoneal Macrophage ◽  
Space Shuttle ◽  
Marrow Cell ◽  
Interleukin 2 ◽  
Plasma Corticosterone ◽  
Interferon Γ ◽  
Experimental Models ◽  
Sprague Dawley ◽  
Immunological Parameters ◽  
Immunological Responses

Sprague-Dawley rats were subjected to two 8-day spaceflights on the space shuttle. Rats housed in the National Aeronautics and Space Administration’s animal enclosure were injected (iv or sc) with pegylated interleukin-2 (PEG-IL-2) or a placebo. We tested the hypothesis that PEG-IL-2 would ameliorate some of the effects of spaceflight. We measured body and organ weights; blood cell differentials; plasma corticosterone; colony-forming units (macrophage and granulocyte macrophage); lymphocyte mitogenic, superantigenic, and interferon-γ responses; bone marrow cell and peritoneal macrophage cytokine secretion; and bone strength and mass. Few immunological parameters were affected by spaceflight. However, some spaceflight effects were observed in each flight. Specifically, peritoneal macrophage spontaneous secretion of tumor necrosis factor-α occurred in the first but not in the second flight. A significant monocytopenia and lymphocytopenia were detected in the second but not in the first flight. The second mission produced bone changes more consistent with past spaceflight investigations. PEG-IL-2 did not appear to be beneficial; however, this was mostly due to the lack of spaceflight effects. These studies reflect the difficulty in reproducing experimental models by using current space shuttle conditions.

Influence of spaceflight on the production of interleukin-3 and interleukin-6 by rat spleen and thymus cells

1995 ◽  
Vol 78 (3) ◽  
pp. 810-813 ◽  
Author(s):  
E. S. Miller ◽  
D. A. Koebel ◽  
G. Sonnenfeld
Keyword(s):  
Cell Line ◽  
Space Shuttle ◽  
Biologically Active ◽  
Sprague Dawley ◽  
Spleen Cells ◽  
Interleukin 3 ◽  
Sprague Dawley Rats ◽  
Dependent Cell ◽  
Thymus Cells ◽  
Stimulating Factor

Six adult male Sprague-Dawley rats were flown on the 7-day US space shuttle mission STS-54. After flight, the spleen and thymus from each animal were assayed for the capacity to secrete the cytokines interleukin-3 (IL-3) and IL-6. Spleen and thymus cells (5 x 10(6)/ml) were incubated for 48 h in the presence of 5 micrograms/ml of concanavalin A or 2 micrograms/ml of bacterial lipopolysaccharide to stimulate the production of IL-3 and IL-6. IL-3 activity was measured using the IL-3/colony-stimulating-factor-dependent cell line 32D. IL-6 activity was measured using the IL-6-dependent cell line 7TD1. Spleen and thymus cells harvested from flown rats secreted significantly higher titers of biologically active IL-3 compared with ground control rats. Spaceflight significantly enhanced IL-6 production by thymus, but not spleen, cells. The results of this study demonstrate that spaceflight can enhance the production of certain cytokines by cells of the immune system.

scholarly journals Sex-Dependent Effect of Melatonin on Systemic Erythematosus Lupus Developed in Mrl/Mpj-Faslpr Mice: It Ameliorates the Disease Course in Females, whereas It Exacerbates It in Males

Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 1717-1724 ◽  
Author(s):  
Antonio J. Jimenez-Caliani ◽  
Silvia Jimenez-Jorge ◽  
Patrocinio Molinero ◽  
Jose M. Fernandez-Santos ◽  
Ines Martin-Lacave ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Lupus Erythematosus ◽  
Chronic Administration ◽  
Interferon Γ ◽  
Total Serum ◽  
Male Mice ◽  
Immunological Parameters ◽  
Female Mice ◽  
Spleen And Lymph Nodes ◽  
Nitrite Nitrate

In this study, the effect of chronic administration of melatonin on MRL/MpJ-Faslpr mice has been studied. These mice spontaneously develop an autoimmune disease that has many features resembling human systemic lupus erythematosus. In fact, histological studies showed that all female mice and most male mice exhibited glomerular abnormalities, arteritic lesions, and cellular interstitial inflammatory infiltrate ranging from mild to severe patterns. Treatment with melatonin improved the histological pattern in females and worsened it in males. Moreover, female mice treated with melatonin showed a diminution of titers of total serum IgG, IgM, and anti-double-stranded DNA and anti-CII autoantibodies; a decrease in proinflammatory cytokines (IL-2, IL-6, interferon-γ, TNF-α, and IL-1β), an increase in antiinflammatory cytokines (IL-10), and a decrease in nitrite/nitrate. In male mice, treatment with melatonin exhibited the opposite effect, worsening all the immunological parameters with an elevation of titers of autoantibodies and a prevalence of proinflammatory vs. antiinflammatory cytokines. Similar results were obtained when lymphocytes from spleen and lymph nodes were cultured. Again, melatonin treatment in females decreased proinflammatory cytokines and increased antiinflammatory cytokines produced by lymphocytes; in males, the effect was the opposite. These findings suggest that melatonin action in MRL/MpJ-Faslpr mice is gender dependent, probably through modulation and inhibition of sex hormones.

Immunomodulatory Effects of Feed-Borne Fusarium Mycotoxins in Chickens Infected with Coccidia

2008 ◽  
Vol 233 (11) ◽  
pp. 1411-1420 ◽  
Author(s):  
George N. Girgis ◽  
Shayan Sharif ◽  
John R. Barta ◽  
Herman J. Boermans ◽  
Trevor K. Smith
Keyword(s):  
Gene Expression ◽  
Mononuclear Cells ◽  
Control Diet ◽  
Recovery Period ◽  
Interferon Γ ◽  
Total Serum ◽  
Infection Model ◽  
Post Inoculation ◽  
Fusarium Mycotoxins ◽  
Immune Parameters

The potential for Fusarium mycotoxins to modulate immunity was studied in chickens raised to 10 weeks of age using an enteric coccidial infection model. Experimental diets included: control, diets containing grains naturally contaminated with Fusarium mycotoxins, and diets containing contaminated grains + 0.2% polymeric glucomannan mycotoxin adsorbent (GMA). Contaminated diets contained up to 3.8 μg/g deoxynivalenol (DON), 0.3 μg/g 15-acetyl DON and 0.2 μg/g zearalenone. An optimized mixture (inducing lesions without mortality) of Eimeria acervulina, E. maxima and E. tenella was used to challenge birds at 8 weeks of age. Immune parameters were studied prior to challenge, at the end of the challenge period (7 days post-inoculation, PI), and at the end of the recovery period (14 days PI). Total serum immunoglobulin (Ig) A and IgG concentrations in challenged birds fed the contaminated diet were higher than controls at the end of the challenge period. Serum concentration of IgA, but not IgG, was significantly decreased at the end of the recovery period in birds fed the contaminated diet. The percentage of CD4+ and CD8+ cell populations in blood mononuclear cells decreased significantly at the end of the challenge period in birds fed the control or the contaminated diet compared to their percentages prior to challenge. The pre-challenge percentage of CD8+ population was restored at the end of the recovery period only in birds fed the control diet. Interferon-γ (IFN-γ) gene expression in caecal tonsils was up-regulated in challenged birds fed the contaminated diet at the end of the challenge period. No significant effect of diet was observed on oocyst counts despite the changes in the studied immune parameters. It was concluded that Fusarium mycotoxins modulate the avian immune system. This modulation involves alteration of gene expression but apparently does not enhance susceptibility or resistance to a primary coccidial challenge.

scholarly journals Interleukin-18 (Interferon-γ–inducing Factor) Is Produced by Osteoblasts and Acts Via Granulocyte/Macrophage Colony-stimulating Factor and Not Via Interferon-γ to Inhibit Osteoclast Formation

1997 ◽  
Vol 185 (6) ◽  
pp. 1005-1012 ◽  
Author(s):  
Nobuyuki Udagawa ◽  
Nicole J. Horwood ◽  
Jan Elliott ◽  
Alan Mackay ◽  
Jane Owens ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Interferon Γ ◽  
Spleen Cells ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Ifn Γ ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Deficient Mice ◽  
Csf Production

We have established by differential display polymerase chain reaction of mRNA that interleukin (IL)-18 is expressed by osteoblastic stromal cells. The stromal cell populations used for comparison differed in their ability to promote osteoclast-like multinucleated cell (OCL) formation. mRNA for IL-18 was found to be expressed in greater abundance in lines that were unable to support OCL formation than in supportive cells. Recombinant IL-18 was found to inhibit OCL formation in cocultures of osteoblasts and hemopoietic cells of spleen or bone marrow origin. IL-18 inhibited OCL formation in the presence of osteoclastogenic agents including 1α,25-dihydroxyvitamin D3, prostaglandin E2, parathyroid hormone, IL-1, and IL-11. The inhibitory effect of IL-18 was limited to the early phase of the cocultures, which coincides with proliferation of hemopoietic precursors. IL-18 has been reported to induce interferon-γ (IFN-γ) and granulocyte/macrophage colony-stimulating factor (GM–CSF) production in T cells, and both agents also inhibit OCL formation in vitro. Neutralizing antibodies to GM–CSF were able to rescue IL-18 inhibition of OCL formation, whereas neutralizing antibodies to IFN-γ did not. In cocultures with osteoblasts and spleen cells from IFN-γ receptor type II–deficient mice, IL-18 was found to inhibit OCL formation, indicating that IL-18 acted independently of IFN-γ production: IFN-γ had no effect in these cocultures. Additionally, in cocultures in which spleen cells were derived from receptor-deficient mice and osteoblasts were from wild-type mice and vice versa, we identified that the target cells for IFN-γ inhibition of OCL formation were the hemopoietic cells. The work provides evidence that IL-18 is expressed by osteoblasts and inhibits OCL formation via GM–CSF production and not via IFN-γ production.

scholarly journals β2-1 Fructans have a bifidogenic effect in healthy middle-aged human subjects but do not alter immune responses examined in the absence of an in vivo immune challenge: results from a randomised controlled trial

2012 ◽  
Vol 108 (10) ◽  
pp. 1818-1828 ◽  
Author(s):  
Amy R. Lomax ◽  
Lydia V. Y. Cheung ◽  
Kieran M. Tuohy ◽  
Paul S. Noakes ◽  
Elizabeth A. Miles ◽  
...  
Keyword(s):  
Immune Responses ◽  
Human Subjects ◽  
Killer Cell ◽  
Total Serum ◽  
Immune Challenge ◽  
Middle Aged ◽  
Immune Parameters ◽  
Faecal Samples ◽  
Bifidogenic Effect

β2-1 fructans are considered to be prebiotics. Current literature indicates that β2-1 fructans may modulate some aspects of immune function, improve the host's ability to respond to certain intestinal infections, and modify some inflammatory outcomes in human subjects. However, there is a need to find out more about the modulation of immune markers by β2-1 fructans in humans. Healthy human subjects aged 45–65 years were randomly allocated to β2-1 fructans (Orafti® Synergy1; 8 g/d; n 22) or the digestible carbohydrate maltodextrin as placebo (n 21) for 4 weeks. Blood, saliva and faecal samples were collected at study entry and after 4 weeks. Immune parameters were measured using the blood and saliva samples and bifidobacteria were measured in the faecal samples. Faecal bifidobacteria numbers increased in the Orafti® Synergy1 group (P < 0·001) and were different at 4 weeks from numbers in the placebo group (P = 0·001). There was no significant effect of Orafti® Synergy1 on any of the immune parameters measured (blood immune cell subsets, total serum Ig, salivary IgA, neutrophil and monocyte phagocytosis of Escherichia coli and respiratory burst in response to E. coli or phorbol ester, natural killer cell activity, T cell activation and proliferation, production of six cytokines by T cells). It is concluded that, compared with maltodextrin, Orafti® Synergy1 has a bifidogenic effect in healthy middle-aged human subjects but does not alter immune responses examined in the absence of an in vivo immune challenge.

scholarly journals Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040426
Author(s):  
Gyaviira Nkurunungi ◽  
Ludoviko Zirimenya ◽  
Jacent Nassuuna ◽  
Agnes Natukunda ◽  
Prossy N Kabuubi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Low Income ◽  
Controlled Trial ◽  
Interferon Γ ◽  
Population Differences ◽  
Vaccine Response ◽  
Vaccine Responses ◽  
Helminth Infections ◽  
Registration Number ◽  
Randomised Controlled

IntroductionSeveral licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response.Methods and analysisWe have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9–17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day ‘zero’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses.Ethics and disseminationEthics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration numberISRCTN60517191.

scholarly journals Construction of Recombinant Human GM-CSF and GM-CSF-ApoA-I Fusion Protein and Evaluation of Their Biological Activity

2021 ◽  
Vol 14 (5) ◽  
pp. 459
Author(s):  
Mariya Pykhtina ◽  
Svetlana Miroshnichenko ◽  
Vladimir Romanov ◽  
Antonina Grazhdantseva ◽  
Galina Kochneva ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
E Coli ◽  
Gm Csf ◽  
Human Apolipoprotein ◽  
Proliferative Effect ◽  
Erythroleukemia Cells ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

In this study, two strains of the yeast P. pastoris were constructed, one of which produced authentic recombinant human granulocyte-macrophage colony-stimulating factor (ryGM-CSF), and the other was a chimera consisting of ryGM-CSF genetically fused with mature human apolipoprotein A-I (ApoA-I) (ryGM-CSF-ApoA-I). Both forms of the cytokine were secreted into the culture medium. The proteins’ yield during cultivation in flasks was 100 and 60 mg/L for ryGM-CSF and ryGM-CSF-ApoA-I, respectively. Both forms of recombinant GM-CSF stimulated the proliferation of human TF-1 erythroleukemia cells; however, the amount of chimera required was 10-fold that of authentic GM-CSF to induce a similar proliferative effect. RyGM-CSF exhibited a 2-fold proliferative effect on BFU-E (burst-forming units—erythroid) at a concentration 1.7 fold less than non-glycosylated E. coli-derived GM-CSF. The chimera together with authentic ryGM-CSF increased the number of both erythroid precursors and BMC granulocytes after 48 h of incubation of human bone marrow cells (BMCs). In addition, the chimeric form of ryGM-CSF was more effective at increasing the viability of the total amount of BMCs, decreasing apoptosis compared to the authentic form. ryGM-CSF-ApoA-I normalized the proliferation, maturation, and segmentation of neutrophils within the physiological norm, preserving the pool of blast cells under conditions of impaired granulopoiesis. The chimera form of GM-CSF exhibited the properties of a multilinear growth factor, modulating the activity of GM-CSF and, perhaps, it may be more suitable for the normalization of granulopoiesis.

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