scholarly journals Immunomodulatory Effects of Inactivated Parapoxvirus Ovis (Orf Virus) on Human Peripheral Immune Cells: Induction of Cytokine Secretion in Monocytes and Th1-Like Cells

2004 ◽  
Vol 78 (17) ◽  
pp. 9400-9411 ◽  
Author(s):  
Astrid Friebe ◽  
Angela Siegling ◽  
Sonja Friederichs ◽  
Hans-Dieter Volk ◽  
Olaf Weber

ABSTRACT Inactivated parapoxvirus ovis (Orf virus; PPVO) recently displayed strong immunostimulating and modulating capacities in several animal models for acute and chronic virus infections through the induction of gamma interferon (IFN-γ) as a key mediator of antiviral activity. The data presented in this work demonstrate that inactivated PPVO has strong effects on cytokine secretion by human immune cells, including the upregulation of inflammatory and Th1-related cytokines (IFN-γ, tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], IL-8, IL-12, and IL-18) as well as anti-inflammatory and Th2-related cytokines (IL-4, IL-10, and IL-1 receptor antagonist [IL-1ra]). Studies on the mechanism of action revealed virus particles to be the effective components of the preparation. The virus particles activate monocytes or other antigen-presenting cells (APC), e.g., plasmacytoid dendritic cells, through signaling over CD14 and a Toll-like receptor and the intracellular presence of certain PPVO-specific components. The activation of monocytes or APC is followed by the release of early proinflammatory cytokines (TNF-α, IL-6, and IL-8) as well as the Th1-related cytokines IL-12 and IL-18. Both IL-18 and IL-12 are involved in PPVO-mediated IFN-γ release by T cells and/or NK cells. The proinflammatory response is accompanied by the induction of anti-inflammatory and Th2-related cytokines (IL-4, IL-10, and IL-1ra), which exert a limiting efffect on the inflammatory response induced by PPVO. We conclude that the induction of a natural immune response with physiologically significant amounts of different cytokines and with antiviral potential might provide advantages over existing antiviral immunotherapies.

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 338 ◽  
Author(s):  
Tzu-He Yeh ◽  
Jin-Yuarn Lin

To clarify the effects of steam distilled essential oils (SDEO) from herbs used in traditional Chinese medicine on immune functions, two potential herbs, Acorus gramineusand (AG) and Euodia ruticarpa (ER) cultivated in Taiwan, were selected to assess their immunomodulatory effects using mouse primary splenocytes and peritoneal macrophages. T helper type 1 lymphocytes (Th1) (IL-2), Th2 (IL-5), pro-inflammatory (TNF-α) and anti-inflammatory (IL-10) cytokines secreted by correspondent immune cells treated with SDEO samples were determined using enzyme-linked immunosorbent assay. The total amounts of potential phytochemicals, including total flavonoids, polyphenols and saponins, in these two selected SDEOs were measured and correlated with cytokine levels secreted by immune cells. Our results evidenced that ER SDEO is rich in total flavonoids, polyphenols and saponins. Treatments with AG and ER SDEO significantly (p < 0.05) increased IL-5/IL-2 (Th2/Th1) cytokine secretion ratios by splenocytes, suggesting that both AG and ER SDEO have the Th2-polarization property and anti-inflammatory potential. In addition, AG and ER SDEO, particularly ER SDEO, markedly decreased TNF-α/IL-10 secretion ratios by macrophages in the absence or presence of lipopolysaccharide (LPS), exhibiting substantial effects on spontaneous and LPS-induced inflammation. Significant correlations were found between the total polyphenols, flavonoids or saponins content in the two selected SDEOs and Th1/Th2 immune balance or anti-inflammatory ability in linear, non-linear or biphasic manners, respectively. In conclusion, our results suggest that AG and ER, particularly ER, SDEO have immunomodulatory potential in shifting the Th1/Th2 balance toward Th2 polarization in splenocytes and inhibiting inflammation in macrophages in the absence or presence of LPS.


2017 ◽  
Vol 96 (5) ◽  
pp. 586-594 ◽  
Author(s):  
Y. Liu ◽  
T. Zhang ◽  
C. Zhang ◽  
S.S. Jin ◽  
R.L. Yang ◽  
...  

Immunologic response plays an important role in orthodontic tooth movement (OTM) and relapse. Nonsteroidal anti-inflammatory drugs, such as aspirin, affect immune cells and clinical orthodontic treatment. However, the mechanisms by which nonsteroidal anti-inflammatory drugs regulate immune cells to affect orthodontic relapse are unclear. In this study, male Sprague-Dawley rats were grouped as relapse and relapse + aspirin for 10 d after 14 d of OTM. Silicone impressions of the rats’ maxillary dentitions were obtained to record the distance of OTM at the indicated time point. CD4+ T lymphocytes in spleen were examined by flow cytometry. Serum levels of type 1 T-helper (Th1) cell–associated cytokines tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ) were determined through enzyme-linked immunosorbent assay. The effects of aspirin on CD4+ T and Th1 cells were also analyzed in vitro. Aspirin treatment significantly reduced the relapse rate. More interestingly, injection of CD25 neutralizing antibody basiliximab or TNF-α inhibitor etanercept can significantly reduce the relapse rate as well. Correspondingly, aspirin treatment significantly accelerated the decrease of orthodontic force–induced secretion of TNF-α and IFN-γ in serum and the expression of TNF-α and IFN-γ in periodontal ligament during relapse. Furthermore, aspirin treatment in vitro significantly repressed the differentiation of CD4+ T and Th1 cells. Overall, results indicated that aspirin treatment can block orthodontic relapse by regulating Th1 cells.


2003 ◽  
Vol 70 (2) ◽  
pp. 165-173 ◽  
Author(s):  
Michael Schultz ◽  
Hans-Jörg Linde ◽  
Norbert Lehn ◽  
Kurt Zimmermann ◽  
Johannes Grossmann ◽  
...  

Probiotic microorganisms, especially lactic acid bacteria, are effective in the treatment of infectious diarrhoeal diseases and experimental colitis. Although the mechanisms by which these organisms exert their anti-inflammatory effects are largely unknown, immunomodulating effects are suggested. The objective of this study was to examine the effect of a 5-week oral administration of Lactobacillus rhamnosus subspecies GG (Lb. GG) on the cellular immune response to intestinal microorganisms in ten healthy volunteers. Peripheral blood cells (PB) were stimulated with either ‘self’ or ‘non-self’ preparations of faecal samples and isolated Bacteroides fragilis group-organisms (Bfg) or Escherichia coli (Esch. coli), and pro- and anti-inflammatory cytokines (IL-10, IL-4, IL-6, IFN-γ, TNF-α) were measured in the culture supernatant. CD4+ T-lymphocyte activation was determined by measurement of intracellular ATP following lysis of the cells. The activational response of CD4+ T-lymphocytes towards isolated and heat-inactivated intestinal organisms was increased after the probiotic treatment. Additionally, TNF-α, IL-6 and in part IFN-γ cytokine secretion by PB cells following stimulation with whole stool preparations and single members of the flora was significantly decreased, whereas the IL-10 and in part IL-4 cytokine secretion was increased at the end of the study. In contrast, the activational response of CD4+ T-lymphocytes following stimulation with whole ‘non-self’ intestinal flora was higher than by ‘self’ intestinal flora, but both responses showed a trend towards a reduction at the end of the study. This study documents a direct effect by Lb. GG on the cellular immune system of healthy volunteers and offers a promising tool to investigate systemic immunomodulation due to oral administration of probiotic microorganisms.


2004 ◽  
Vol 48 (8) ◽  
pp. 2793-2798 ◽  
Author(s):  
C. A. Gogos ◽  
A. Skoutelis ◽  
A. Lekkou ◽  
E. Drosou ◽  
I. Starakis ◽  
...  

ABSTRACT In the present study the effect of ciprofloxacin versus ceftazidime on concentrations of pro- and anti-inflammatory cytokines in the sera of patients with severe sepsis was evaluated. The study included 58 previously healthy patients suffering from severe sepsis caused by gram-negative bacteria, treated with either ciprofloxacin or ceftazidime after thorough clinical and microbiological evaluation and followed up for clinical outcome. Levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1b (IL-1b), IL-6, and IL-8 and of the anti-inflammatory cytokine IL-10, as well as of IL-1 receptor antagonist and soluble TNF receptors I and II, in serum were measured at baseline and 24 and 48 h after the first antimicrobial dose. Mean SAPS-II scores, development of septic shock, and mortality rates were similar in the two groups (43.2 ± 9.2, 21.4%, and 14.3% in the ceftazidime group versus 49.8 ± 11.3, 20%, and 13.3% in the ciprofloxacin group). Serum TNF-α and IL-6 levels at 24 and 48 h were significantly lower in the ciprofloxacin group, while the IL-10/TNF-α ratio was significantly higher, than those for the ceftazidime group. Among patients with high baseline TNF-α levels, there were significant increases in the IL-10/TNF-α ratio at both 24 and 48 h over that at admission for the ciprofloxacin group, while no differences were noted in the ceftazidime group. These results indicate that ciprofloxacin may have an immunomodulatory effect on septic patients by attenuating the proinflammatory response, while there is no evidence that differences in the cytokines measured have any impact on the final outcome.


2006 ◽  
Vol 75 (2) ◽  
pp. 820-829 ◽  
Author(s):  
Edhyana Sahiratmadja ◽  
Bachti Alisjahbana ◽  
Tjitske de Boer ◽  
Iskandar Adnan ◽  
Anugrah Maya ◽  
...  

ABSTRACT Pro- and anti-inflammatory cytokines and their signaling pathways play key roles in protection from and pathogenesis of mycobacterial infection, and their balance and dynamic changes may control or predict clinical outcome. Peripheral blood cells' capacity to produce proinflammatory (tumor necrosis factor alpha [TNF-α], interleukin-12/23p40 [IL-12/23p40], and gamma interferon [IFN-γ]) and anti-inflammatory (IL-10) cytokines in response to Mycobacterium tuberculosis or unrelated stimuli (lipopolysaccharide, phytohemagglutinin) was studied in 93 pulmonary tuberculosis (TB) patients and 127 healthy controls from Indonesia. Their cells' ability to respond to IFN-γ was examined to investigate whether M. tuberculosis infection can also inhibit IFN-γ receptor (IFN-γR) signaling. Although there was interindividual variability in the observed responses, the overall results revealed that M. tuberculosis-induced TNF-α and IFN-γ levels showed opposite trends. Whereas TNF-α production was higher in active-TB patients than in controls, IFN-γ production was strongly depressed during active TB, correlated inversely with TB disease severity, and increased during therapy. By contrast, mitogen-induced IFN-γ production, although lower in patients than in controls, did not change during treatment, suggesting an M. tuberculosis-specific and reversible component in the depression of IFN-γ. Depressed IFN-γ production was not due to decreased IL-12/IL-23 production. Importantly, IFN-γ-inducible responses were also significantly depressed during active TB and normalized during treatment, revealing disease activity-related and reversible impairment in IFN-γR signaling in TB. Finally, IFN-γ/IL-10 ratios significantly correlated with TB cure. Taken together, these results show that M. tuberculosis-specific stimulation of IFN-γ (but not TNF-α) production and IFN-γR signaling are significantly depressed in active TB, correlate with TB disease severity and activity, and normalize during microbiological TB cure. The depression of both IFN-γ production and IFN-γR signaling may synergize in contributing to defective host control in active TB.


2012 ◽  
Vol 81 (3) ◽  
pp. 740-752 ◽  
Author(s):  
Brian M. Gray ◽  
Clinton A. Fontaine ◽  
Sara A. Poe ◽  
Kathryn A. Eaton

ABSTRACTDisease due to the gastric pathogenHelicobacter pylorivaries in severity from asymptomatic to peptic ulcer disease and cancer. Accumulating evidence suggests that one source of this variation is an abnormal host response. The goal of this study was to use a mouse model ofH. pylorigastritis to investigate the roles of regulatory T cells (Treg) as well as proinflammatory T cells (Th1 and Th17) in gastritis, gastric T cell engraftment, and gastric cytokine production. Our results support published data indicating that severe gastritis in T cell recipient mice is due to failure of Treg engraftment, that Treg ameliorate gastritis, and that the proinflammatory response is attributable to interactions between several cell subsets and cytokines. We confirmed that gamma interferon (IFN-γ) is essential for induction of gastritis but showed that IFN-γ-producing CD4 T cells are not necessary. Interleukin 17A (IL-17A) also contributed to gastritis, but to a lesser extent than IFN-γ. Tumor necrosis factor alpha (TNF-α) and IL-17F were also elevated in association with disease. These results indicate that whileH. pylori-specific CD4+T cells and IFN-γ are both essential for induction of gastritis due toH. pylori, IFN-γ production by T cells is not essential. It is likely that other proinflammatory cytokines, such as IL-17F and TNF-α, shown to be elevated in this model, also contribute to the induction of disease. We suggest that gastritis due toH. pyloriis associated with loss of immunoregulation and alteration of several cytokines and cell subsets and cannot be attributed to a single immune pathway.


Pharmacology ◽  
2019 ◽  
Vol 104 (3-4) ◽  
pp. 187-195 ◽  
Author(s):  
Xing Li ◽  
Peigen Xie ◽  
Yu Hou ◽  
Shudong Chen ◽  
Peiheng He ◽  
...  

Background/Aims: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats. Methods: TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1β [IL-1β], ­IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism. Results: TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1β, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway. Conclusion: TAN might have potential as a therapeutic agent for the treatment of RA.


2021 ◽  
Vol 7 (3) ◽  
pp. 205521732110323
Author(s):  
Kouichi Ito ◽  
Naoko Ito ◽  
Sudhir K Yadav ◽  
Shradha Suresh ◽  
Yong Lin ◽  
...  

Background Many RRMS patients who had been treated for over 20 years with GA 20 mg/ml daily (GA20) switched to 40 mg/ml three times-a-week (GA40) to reduce injection-related adverse events. Although GA40 is as effective as GA20 in reducing annualized relapse rate and MRI activity, it remains unknown how switching to GA40 from GA20 affects the development of pathogenic and regulatory immune cells. Objective To investigate the difference in immunological parameters in response to GA20 and GA40 treatments. Methods We analyzed five pro-inflammatory cytokines (IL-1β, IL-23, IL-12, IL-18, TNF-α), and three anti-inflammatory/regulatory cytokines (IL-10, IL-13, and IL-27) in serum. In addition, we analyzed six cytokines (IFN-γ, IL-17A, GM-CSF, IL-10, IL-6, and IL-27) in cultured PBMC supernatants. The development of Th1, Th17, Foxp3 Tregs, M1-like, and M2-like macrophages were examined by flow cytometry. Samples were analyzed before and 12 months post switching to GA40 or GA20. Results Pro- and anti-inflammatory cytokines were comparable between the GA40 and GA20 groups. Development of Th1, Th17, M1-like macrophages, M2-like macrophages, and Foxp3 Tregs was also comparable between the two groups. Conclusions The immunological parameters measured in RRMS patients treated with GA40 three times weekly are largely comparable to those given daily GA20 treatment.


2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Barbara Misme-Aucouturier ◽  
Marjorie Albassier ◽  
Nidia Alvarez-Rueda ◽  
Patrice Le Pape

ABSTRACT A delayed type of multicellular process could be crucial during chronic candidiasis in determining the course of infection. This reaction, consisting of organized immune cells surrounding the pathogen, initiates an inflammatory response to avoid fungal dissemination. The goal of the present study was to examine, at an in vitro cellular scale, Candida and human immune cell interaction dynamics during a long-term period. By challenging human peripheral blood immune cells from 10 healthy donors with 32 Candida albicans and non-albicans (C. glabrata, C. tropicalis, C. parapsilosis, C. dubliniensis, C. lusitaniae, C. krusei, and C. kefyr) clinical isolates, we showed that Candida spp. induced the formation of granuloma-like structures within 6 days after challenge, but their sizes and the respective fungal burdens differed according to the Candida species. These two parameters are positively correlated. Phenotypic characteristics, such as hypha formation and higher axenic growth rate, seem to contribute to yeast persistence within granuloma-like structures. We showed an interindividual variability of the human response against Candida spp. Higher proportions of neutrophils and elevated CD4+/CD8+ T cell ratios during the first days after challenge were correlated with early production of gamma interferon (IFN-γ) and associated with controlled infection. In contrast, the persistence of Candida could result from upregulation of proinflammatory cytokines such as interleukin-6 (IL-6), IFN-γ, and tumor necrosis factor alpha (TNF-α) and a poor anti-inflammatory negative feedback (IL-10). Importantly, regulatory subsets of NK cells and CD4lo CD8hi doubly positive (DP) lymphocytes at late stage infiltrate granuloma-like structures and could correlate with the IL-10 and TNF-α production. These data offer a base frame to explain cellular events that guide infection control or fungal persistence.


2010 ◽  
Vol 78 (3) ◽  
pp. 1353-1363 ◽  
Author(s):  
Antara Banerjee ◽  
Frederik Stevenaert ◽  
Kalyan Pande ◽  
Erik Haghjoo ◽  
Svetlana Antonenko ◽  
...  

ABSTRACT Paired immunoglobulin-like type 2 receptors (PILRs) inhibitory PILRα and activating PILRβ are predominantly expressed on myeloid cells. Their functions in host defense and inflammation are largely unknown, and in this study, we evaluated their roles in an acute Staphylococcus aureus pneumonia model. Compared to their respective controls, Pilrb −/− mice or mice in which PILRα was activated with an agonistic antibody showed improved clearance of pulmonary staphylococci and improved survival. These mice had reduced serum or bronchoalveolar lavage fluid levels of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6 and elevated levels of gamma interferon (IFN-γ), IL-12, and IL-10. In contrast, mice in which PILRβ was activated had increased lung bacterial burdens and higher mortality coupled with an intense proinflammatory response with highly elevated levels of IL-1β, TNF-α, and IL-6. Treatment groups with reduced bacterial burdens had higher levels of Keratinocyte-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2), and MIP-1α in bronchoalveolar lavage fluid and an increased influx of neutrophils and macrophages to the lungs. Consistent with our in vivo findings, bone marrow-derived macrophages from Pilrb −/− mice released significantly less IL-1β and TNF-α and more IFN-γ and IL-12 than did the wild-type macrophages when directly stimulated with heat-killed S. aureus. To our knowledge, this is the first evidence that S. aureus directly interacts with PILRβ. It provides a mechanism by which manipulating the balance in favor of an inhibitory PILR signal, by activation of PILRα or deletion of PILRβ, helps to control acute S. aureus-mediated pneumonia and attenuate the inflammatory response. These results highlight the importance of PILRs in innate immunity and the control of inflammation.


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