scholarly journals Intravenous Immunoglobulin Therapy Eliminates Candida albicans and Maintains Intestinal Homeostasis in a Murine Model of Dextran Sulfate Sodium-Induced Colitis

2019 ◽  
Vol 20 (6) ◽  
pp. 1473 ◽  
Author(s):  
Rogatien Charlet ◽  
Boualem Sendid ◽  
Srini Kaveri ◽  
Daniel Poulain ◽  
Jagadeesh Bayry ◽  
...  

Intravenous immunoglobulin (IVIg) therapy has diverse anti-inflammatory and immunomodulatory effects and has been employed successfully in autoimmune and inflammatory diseases. The role of IVIg therapy in the modulation of intestinal inflammation and fungal elimination has not been yet investigated. We studied IVIg therapy in a murine model of dextran sulfate sodium (DSS)-induced colitis. Mice received a single oral inoculum of Candida albicans and were exposed to DSS treatment for 2 weeks to induce colitis. All mice received daily IVIg therapy starting on day 1 for 7 days. IVIg therapy not only prevented a loss of body weight caused by the development of colitis but also reduced the severity of intestinal inflammation, as determined by clinical and histological scores. IVIg treatment significantly reduced the Escherichia coli, Enterococcus faecalis, and C. albicans populations in mice. The beneficial effects of IVIg were associated with the suppression of inflammatory cytokine interleukin (IL)-6 and enhancement of IL-10 in the gut. IVIg therapy also led to an increased expression of peroxisome proliferator-activated receptor gamma (PPARγ), while toll-like receptor 4 (TLR-4) expression was reduced. IVIg treatment reduces intestinal inflammation in mice and eliminates C. albicans overgrowth from the gut in association with down-regulation of pro-inflammatory mediators combined with up-regulation of anti-inflammatory cytokines.

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2630
Author(s):  
Jiah Yeom ◽  
Seongho Ma ◽  
Jeong-Keun Kim ◽  
Young-Hee Lim

Colitis causes destruction of the intestinal mucus layer and increases intestinal inflammation. The use of antioxidants and anti-inflammatory agents derived from natural sources has been recently highlighted as a new approach for the treatment of colitis. Oxyresveratrol (OXY) is an antioxidant known to have various beneficial effects on human health, such as anti-inflammatory, antibacterial activity, and antiviral activity. The aim of this study was to investigate the therapeutic effect of OXY in rats with dextran sulfate sodium (DSS)-induced acute colitis. OXY ameliorated DSS-induced colitis and repaired damaged intestinal mucosa. OXY downregulated the expression of pro-inflammatory cytokine genes (TNF-α, IL-6, and IL-1β) and chemokine gene MCP-1, while promoting the production of anti-inflammatory cytokine IL-10. OXY treatment also suppressed inflammation via inhibiting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in the colon, as well as the activity of myeloperoxidase (MPO). OXY exhibited anti-apoptotic effects, shifting the Bax/Bcl-2 balance. In conclusion, OXY might improve DSS-induced colitis by restoring the intestinal mucus layer and reducing inflammation within the intestine.


1997 ◽  
Vol 108 (2) ◽  
pp. 340-345 ◽  
Author(s):  
N. SHINTANI ◽  
T. NAKAJIMA ◽  
H. NAKAKUBO ◽  
H. NAGAI ◽  
Y. KAGITANI ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Maraisa Cristina Silva ◽  
Helioswilton Sales-Campos ◽  
Carlo José Freire Oliveira ◽  
Tamires Lopes Silva ◽  
Flávia Batista Ferreira França ◽  
...  

It has been described that the metalloprotease BmooMP-alpha-I purified from Bothrops moojeni snake venom is able to hydrolyze the TNF molecule. However, this observation has been based mainly on in vitro investigation, in addition to molecular modeling and docking approaches. Considering that there is no in vivo study to demonstrate the biological effects of this enzyme, the major aim to the present work was to investigate whether the BmooMP-alpha-I has any anti-inflammatory efficacy by setting up a murine experimental design of colitis induced by dextran sulfate sodium (DSS). For this purpose, C57BL/6 mice were divided into six groups, as follows: (i) animals without intestinal inflammation, (ii) animals without intestinal inflammation treated with BmooMP-alpha-I (50 μg/animal/day), and (iii) animals with intestinal inflammation induced by 3% of DSS, (iv) mice with intestinal inflammation induced by DSS and treated with BmooMP-alpha-I enzyme at the 50, 25, or 12.5 μg/animal/day dosages by intraperitoneal route. Clinical signs of colitis were observed daily for calculating the morbidity scores, cytokine measurements, and histological features. We observed that the animals treated with different doses of the enzyme presented a remarkable improvement of colitis signs, as confirmed by a significant increase of the intestine length in comparison to the DSS group. Also, no difference was observed between the groups treated with the enzyme or vehicle, as the colon length of these animals was slightly lower than that of the group of healthy animals, without induction of intestinal inflammation. The cytokine quantification in supernatants of intestinal tissue homogenates showed a significant reduction of 38% in IFN-gamma levels, when the animals were treated with 50 μg of the BmooMP-alpha-I compared to the animals receiving DSS only. A significant reduction of 39% in TNF levels was also observed in all doses of treatment with BmooMP-alpha-I, in addition to a significant reduction of 35% in the amount of IL-12p40. Histological examinations revealed that the BmooMP-alpha-I 50 μg treated group preserved colon architecture and goblet cells and reduced the ulcer area, when compared with DSS mice, which showed typical inflammatory changes in tissue architecture, such as ulceration, crypt dilation, loss of tissue architecture, and goblet cell depletion, accompanied by a significant cell infiltration. In conclusion, our results suggest that the improvement of clinical scores and histological findings related to BmooMP-alpha-I treatment in this experimental model could be attributed to the metalloprotease ability to modulate cytokine production locally at the inflamed intestine. These findings highlight the potential anti-inflammatory role and effectiveness of this enzyme as a therapeutic alternative in this type of immunopathological condition.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Noboru Yamamoto ◽  
Kaoru Sato ◽  
Takayuki Hoshina ◽  
Masumi Kojiro ◽  
Koichi Kusuhara ◽  
...  

Purpose: Several scoring systems for prediction of non-responsiveness to initial course of intravenous immunoglobulin (IVIG) therapy have been available in the patients diagnosed as Kawasaki disease (KD). However, all non-responders cannot be identified completely by these scoring systems. The aim of this study is to investigate whether ferritin can be a useful marker as a predictor of the patients with KD refractory to IVIG therapy. Materials and Methods: This retrospective study enrolled 63 patients with KD hospitalized at Kitakyushu General Hospital during 2010 to 2013. These patients were divided into IVIG responders (n= 41) and non-responders (n=22). Serum ferritin levels and the scoring systems for prediction of non-responsiveness to initial IVIG treatment were compared between these two groups. Results: Serum ferritin level was significantly elevated in non-responders (p=0.01). The area under the receiver-operating-characteristics curve was 0.698, and the sensitivity and specificity in more than 215 ng/ml of serum ferritin levels was 54.5% and 85.4%, respectively. Two of the three scoring systems for prediction of non-responsiveness to initial IVIG treatment in non-responders were also significantly higher scores than that in responders, but many non-responders had a low score of these scoring systems. Approximately half of the patients with low score of these scoring systems had high serum ferritin level (≧ 215 ng/ml). Conclusion: Serum ferritin level can be a useful marker for the prediction of non-responsiveness to initial IVIG treatment and may be an important complementary marker to the scoring systems for prediction of non-responsiveness to initial IVIG treatment.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Wenhua Xu ◽  
Mingshan Ren ◽  
Swagata Ghosh ◽  
Kai Qian ◽  
Zhaofeng Luo ◽  
...  

Myasthenia gravis (MG) is a CD4+ T cell-dependent autoimmune disease resulting from aberrant immune response mediated by circulating autoantibodies at the neuromuscular junction. Intravenous immunoglobulin (IVIg) is an expensive and commonly used immunotherapeutic approach to treat patients with MG. The mechanisms of actions involved in IVIg treatment, however, remain to be investigated. In an effort to examine the roles of various subsets of CD4+ T cells in the periphery blood of MG and uncover the mechanisms that contribute to the therapeutical effects of IVIg, we first demonstrated that a subset of CD4+ T cells, CTLA-4-expressing regulatory T (Treg) cells, were underrepresented and functionally defective in MG patients. The dynamic profiling during the IVIg therapy course further revealed an inverse relationship between the frequency of CTLA-4+ Treg and the quantitative MG (QMG) score that represents disease severity. Our mechanistic studies indicated that IVIg expands CTLA-4-Treg cells via modulating antigen-presenting dendritic cells (DCs). To determine the molecular defects of CTLA-4 in abnormities of Treg in MG patients, we demonstrated hypermethylation at -658 and -793 CpGs of CTLA-4 promoter in MG Tregs. Interestingly, IVIg therapy significantly reduced the methylation level at these two sites in MG patients. Overall, our study may suggest a role of CTLA-4 in functionally defected Treg cells in MG and its actions involved in IVIg therapy.


2013 ◽  
Vol 5 (3) ◽  
pp. 14 ◽  
Author(s):  
Lale Memmedova ◽  
Elif Azarsiz ◽  
Neslihan Edeer Karaca ◽  
Guzide Aksu ◽  
Necil Kutukculer

Transient hypogammaglobulinemia of infancy (THI) is characterized by recurrent infections and one or more reduced serum immunoglobulin levels. Typically, THI patients recover spontaneously, mostly within 30-40 months of age, but sometimes recovery may be delayed until 5-6 years of age. The use of intravenous immunoglobulin (IVIg) as an alternative to antibiotic prophylaxis remains contraversial also in symptomatic THI patients. In fact, some authors believe that IVIg therapy may cause a delay in the maturation of the humoral immune system because of the interference from passively transfered antibodies. The aim of this study was to investigate the effect of IVIg replacement on recovery from immunodeficiency in THI patients and determine new parameters in order to include these patients in IVIg therapy groups. In this retrospective study, 43 patients (65%) received IVIg replacement therapy while 23 patients (34.8%) showed spontaneous normalization without IVIg. The percentages of patients who had more than six times the number of febrile infections in a year decreased from 91% to 21% in the group receiving IVIg treatment. At admission, before being recruited to IVIg therapy, serum immunoglobulin G (IgG) levels and anti-hemophilus B (Hib) antibody titers were found to be significantly low in cases who were selected for IVIg replacement. The percentages of patients who did not have protective levels of anti-Hib, anti-rubella or anti-rubeola-IgG were also significantly high in IVIg cases. There was no statistically significant difference in the age at which IgG levels normalized between the IVIg and the non-IVIg group. Patients in the IVIg group and non-IVIg group reached normal IgG levels at the age of 42.9±22.0 and 40.7±19.8 months, respectively. In conclusion, IVIg infusions do not cause a delay in the maturation of the immune system in THI patients. Besides the well-established criteria, very low and non-protective specific antibody responses against previously applied vaccines are important factors to consider when selecting patients for IVIg therapy.


Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1895
Author(s):  
Azra Memon ◽  
Bae Yong Kim ◽  
Se-eun Kim ◽  
Yuliya Pyao ◽  
Yeong-Geun Lee ◽  
...  

Background: Phytoncide is known to have antimicrobial and anti-inflammatory properties. Purpose: This study was carried out to confirm the anti-inflammatory activity of two types of phytoncide extracts from pinecone waste. Methods: We made two types of animal models to evaluate the efficacy, an indomethacin-induced gastroenteritis rat model and a dextran sulfate sodium-induced colitis mouse model. Result: In the gastroenteritis experiment, the expression of induced-nitric oxide synthase (iNOS), a marker for inflammation, decreased in the phytoncide-supplemented groups, and gastric ulcer development was significantly inhibited (p < 0.05). In the colitis experiment, the shortening of the colon length and the iNOS expression were significantly suppressed in the phytoncide-supplemented group (p < 0.05). Conclusions: Through this study, we confirmed that phytoncide can directly inhibit inflammation in digestive organs. Although further research is needed, we conclude that phytoncide has potential anti-inflammatory properties in the digestive tract and can be developed as a functional agent.


2021 ◽  
Vol 14 ◽  
pp. 175628642098674
Author(s):  
Shengyao Su ◽  
Qing Liu ◽  
Xueping Zhang ◽  
Xinmei Wen ◽  
Lin Lei ◽  
...  

Background: Intravenous immunoglobulin (IVIG) has been commonly used to treat myasthenia gravis exacerbation, but is still ineffective in nearly 30% of patients. A variable number of tandem repeat (VNTR) polymorphism in the FCGRT gene has been found to reduce the efficiency of IgG biologics. However, whether the polymorphism influences the efficacy of IVIG in generalized myasthenia gravis (MG) patients with exacerbations remains unknown. Methods: The distribution of VNTR genotypes was analyzed in 334 patients with MG. Varied VNTR alleles were determined by capillary electrophoresis and confirmed by Sanger sequencing. Information of endogenous IgG levels were collected in patients without previous immunotherapy ( n = 26). Medical records of patients who received IVIG therapy were retrospectively analyzed for therapeutic outcomes of IVIG treatment ( n = 61). Patients whose Activities of Daily Living scores decreased by 2 or more points on day 14 were considered responders to the treatment. Results: The VNTR3/3 and VNTR2/3 genotypes were detected in 96.7% (323/334) and 3.4% (11/334) patients, respectively. Patients with VNTR2/3 heterozygosity had lower endogenous IgG levels than those with VNTR3/3 homozygosity (9.81 ± 2.61 g/L versus 12.41 ± 2.45g/L, p = 0.016). The response rate of IVIG therapy was 78.7% (48/61). All responders and nine non-responders were VNTR3/3 homozygotes, whereas all the patients with VNTR2/3 genotypes were non-responders ( n = 4). In patients who took IVIG treatments, endogenous IgG levels were significantly lower in non-responders compared with responders (12.93 ± 2.24 g/L versus 8.85 ± 2.69 g/L, p = 0.006), especially in VNTR2/3 heterozygotes (7.86 ± 1.78 g/L, p = 0.001). Conclusion: The VNTR2/3 genotype could influence endogenous IgG levels and serve as a predictive marker for poor responses to IVIG in MG patients.


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