Anti-inflammatory and immunomodulating effects of the bacterial lysate in the <em>in vivo</em> models of aseptic lymphadenitis and pneumococcal pneumonia

Bacterial lysates may produce immunoregulatory effects in the inflammatory diseases that are not directly caused by infectious agents; they may also stimulate the immune response against pathogens which are not a part of the lysate composition. Imudon® is a polyvalent bacterial lysate that is available in orodispersible tablets. However, the influence of this drug product on aseptic inflammation and immune defense against the infectious agents, the antigens of which are not contained in this preparation have not been studied so far. The aim of this study, therefore, was to determine the anti-inflammatory and immunomodulating effects of Imudon® using the models of aseptic lymphadenitis (in Wistar rats) and pneumococcal pneumonia (in Balb/c mice), i.e., the conditions not related to the specific components of the bacterial lysate. Lymphadenitis was induced in rats by administration of λ-carrageenan into a cervical lymph node via an open operative approach. Whereas pneumonia was induced in mice by administering Streptococcus pneumoniae suspension intranasally. The choice of pneumococcus was determined by the absence of pneumococcal antigens in Imudon®, i.e., it cannot be a direct inducer of adaptive immune response against pneumococcal infection. Imudon® was administered intragastrically as a crushed tablet suspension following a therapeutic-preventive regimen (for 14 days daily until the induction of inflammation and for 3 [in the lymphadenitis model] or 5 days [in the model of pneumonia] in three doses thereafter). In the lymphadenitis model, Imudon® demonstrated both local and systemic anti-inflammatory responses manifested in the reduced number of circulating leucocytes and lower TNFα levels and by ameliorated histological features of inflammation in the operated lymph node. In rats, the anti-inflammatory effect was most pronounced when the product was administered at a dose of 2.2 mg/kg (equivalent to a human therapeutic dose) and 6.6 mg/kg. In the model of pneumonia, administration of Imudon® at 4.44 mg/kg (equivalent to a human therapeutic dose) and 13.32 mg/kg demonstrated a trend towards increased survival rate as compared to the control group. On Day 5 after infection Imudon® (4.44 and 13.32 mg/kg) decreased significantly the severity of inflammation and bacterial titer in the lungs. The titer of anti-pneumococcal immunoglobulins A in the bronchoalveolar lavage fluid were found to be higher in the Imudon® treated group (13.32 mg/kg) compared to control group. The results of this study showed high antiinflammatory and immunomodulatory activities of Imudon® and provided an insight into the mechanisms that underlie the clinical effects of this drug in various inflammatory diseases.

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IL-6 Is Not Absolutely Essential for the Development of a TH17 Immune Response after an Aerosol Infection with Mycobacterium tuberculosis H37rv

Cells ◽

10.3390/cells10010009 ◽

2020 ◽

Vol 10 (1) ◽

pp. 9

Author(s):

Kristina Ritter ◽

Jan Christian Sodenkamp ◽

Alexandra Hölscher ◽

Jochen Behrends ◽

Christoph Hölscher

Keyword(s):

Immune Response ◽

Inflammatory Diseases ◽

Mycobacterial Infection ◽

Minor Effect ◽

Mycobacterium Tuberculosis H37rv ◽

Th 17 ◽

Anti Inflammatory ◽

A Minor ◽

Aerosol Infection ◽

Deficient Mice

Anti-inflammatory treatment of chronic inflammatory diseases often increases susceptibility to infectious diseases such as tuberculosis (TB). Since numerous chronic inflammatory and autoimmune diseases are mediated by interleukin (IL)-6-induced T helper (TH) 17 cells, a TH17-directed anti-inflammatory therapy may be preferable to an IL-12-dependent TH1 inhibition in order to avoid reactivation of latent infections. To assess, however, the risk of inhibition of IL-6-dependent TH17-mediated inflammation, we examined the TH17 immune response and the course of experimental TB in IL-6- and T-cell-specific gp130-deficient mice. Our study revealed that the absence of IL-6 or gp130 on T cells has only a minor effect on the development of antigen-specific TH1 and TH17 cells. Importantly, these gene-deficient mice were as capable as wild type mice to control mycobacterial infection. Together, in contrast to its key function for TH17 development in other inflammatory diseases, IL-6 plays an inferior role for the generation of TH17 immune responses during experimental TB.

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Association of interleukin-10 promoter polymorphisms with serofast state after syphilis treatment

Sexually Transmitted Infections ◽

10.1136/sextrans-2018-053753 ◽

2018 ◽

Vol 95 (3) ◽

pp. 163-168 ◽

Cited By ~ 2

Author(s):

Maciej Pastuszczak ◽

Bogdan Jakiela ◽

Anna Wojas-Pelc

Keyword(s):

Immune Response ◽

Interleukin 10 ◽

Control Group ◽

Serological Response ◽

Promoter Polymorphisms ◽

Related Factors ◽

Adequate Treatment ◽

Early Syphilis ◽

Inflammatory Immune Response ◽

Anti Inflammatory

ObjectivesRecent studies suggested that upregulation of anti-inflammatory immune response during early syphilis may be associated with persistence of Treponema pallidum infection despite adequate treatment, resulting in a serofast state. The objective of this study was to determine whether enhanced interleukin (IL)-10-related response during early T. pallidum infection increased the risk of serofast syphilis.MethodsTwo IL10 gene promoter polymorphisms affecting IL-10 production (−1082A>G [rs1800896], −592C>A [rs1800872]) and serum levels of IL-10 were measured in 80 patients with early syphilis before and 6 months after penicillin treatment and in 24 healthy volunteers (control group).ResultsAfter 6 months, patients were stratified based on serological response into two groups: (1) serofast state (n = 28) and (2) serologically cured (n = 52). Pretreatment and post-treatment serum IL-10 levels were significantly higher in patients who remained serofast compared with those who had a serological cure (p<0.001). The GG genotype of the −1082A>G (rs1800896) polymorphism and the CC genotype of the −592C>A (rs1800872) polymorphism were significantly correlated with higher serum IL-10 levels. Moreover, the OR for remaining serofast for carriers of these genotypes was 16.2 (95% CI: 4.1 to 65.0, p<0.0001) and 2.9 (95% CI: 1.4 to 5.9, p=0.002), respectively.ConclusionsWe showed that a pronounced anti-inflammatory immune response may be an important predictor for the serofast state. Additionally, host-related factors such as polymorphisms of immune regulatory genes may influence the risk of remaining serofast after syphilis therapy.

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Pro- and Anti-Inflammatory Cytokines in the First Trimester—Comparison of Missed Miscarriage and Normal Pregnancy

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18168538 ◽

2021 ◽

Vol 18 (16) ◽

pp. 8538

Author(s):

Maciej Kwiatek ◽

Tomasz Gęca ◽

Anna Kwaśniewska

Keyword(s):

Immune Response ◽

Inflammatory Cytokines ◽

First Trimester ◽

Normal Pregnancy ◽

Control Group ◽

Study Group ◽

Tnf Α ◽

Cytokine Levels ◽

Anti Inflammatory ◽

Tgf Β1

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.

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. Full-scale testing of biologically active additive “Ivlaxinˮ in patients with acute inflammatory diseases

Food Processing Techniques and Technology ◽

10.21603/2074-9414-2018-2-143-150 ◽

2019 ◽

Vol 48 (2) ◽

pp. 143-150

Author(s):

Евгения Лобач ◽

Evgeniya Lobach ◽

Андрей Вековцев ◽

Andrey Vekovtsev ◽

Дмитрий Никитюк ◽

...

Keyword(s):

Dietary Supplement ◽

Inflammatory Process ◽

Inflammatory Diseases ◽

Blood Analysis ◽

Biologically Active ◽

Standards Of Care ◽

Control Group ◽

Shortness Of Breath ◽

Therapeutic Treatment ◽

Anti Inflammatory

Clinical tests were carried out in the representative group of patients with focal left-sided pneumonia (5 men and 7 women aged 18–41). Special-use product was included in in-patient department patients’ diet: 2 tablets in the first intake, then 1 tablet 4 times a day. Course of treatment was 21 days. Biologically active dietary supplement was prescribed together with general therapeutic treatment according to generally accepted standards of care. Control group included 15 patients randomized depending on sex and age who took only medicine. The author measured body temperature, studied the results of general blood tests, determined the level of C-reactive protein and seromucoids, performed R-graphy of lungs, electrocardiogram before and after treatment, analyzed clinical symptoms (cough, type of expectoration, shortness of breath). Composition of the special-use product was scientifically justified taking pharmacological characteristics of its ingredients and their active agents into account. Introduction of the biologically active dietary supplement in addition to the prescribed therapeutic treatment gave positive effect in relation to the inflammatory process: the patients could easier clear their throats from expectoration, coughed less frequently, and had less intense shortness of breath. It was evident that symptoms of disease recrudescence decreased. It appeared in the decreased intensity and length of fever. In case of acute respiratory viral infection the biologically active dietary supplement had antipyretic activity due to the anti-exudative effect of its ingredients. The author determined the anti-inflammatory effect and reduction of acute intoxication symptoms taking the results of general blood analysis into account. Patients who took special-use product had lower values of an inflammatory process marker – seromucoids. Tissues restored easily. The tested product has anti-inflammatory, antipyretic and analgesic properties. It can be used in complex treatment of acute inflammatory diseases and recrudescence of chronic inflammatory processes.

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Allium sativum L. (Garlic) Role in Osteoarthritis: A Systematic Review of Clinical Trials

Biointerface Research in Applied Chemistry ◽

10.33263/briac114.1210412119 ◽

2021 ◽

Vol 11 (4) ◽

pp. 12104-12119

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Side Effects ◽

Allium Sativum ◽

Inflammatory Diseases ◽

Control Group ◽

Therapeutic Effects ◽

Inflammatory Factor ◽

Anti Inflammatory ◽

Over Time

Osteoarthritis is a chronic degenerative disease involving the joints and bones, causing their degradation over time. Inflammation, pain, and stiffness in joints are indicators of the disease. Pharmacotherapy cannot always be efficient and may cause side effects. So, adjuncts such as complementary herbs have become of note. Garlic is a herb well-known for its various therapeutic effects such as anti-bacterial, anti-hypertension, antioxidant and anti-inflammatory effects. Due to garlic's widespread use, studying its effects and mechanisms on inflammatory diseases such as osteoarthritis has been noteworthy. We searched Science Direct, Pubmed, Cochrane, and Google Scholar databases for all articles published until October 2020, based on PRISMA. Searched keywords were the following: [(garlic and arthritis), (garlic and osteoarthritis), (Garlic and OA), (Allium sativum and arthritis), (Allium sativum and osteoarthritis), (Allium sativum and OA)]. The results showed garlic, and its constituents have remarkable effects on improving OA symptoms through antioxidant and anti-inflammatory pathways. Our review shows that groups receiving garlic as a treatment showed a significant reduction in pain and inflammatory factor levels and an improved physical function instead of the control group.

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Observing the Anti-oxidant and Anti-inflammatory Effect of Nigella Sativa Combined With Silybum Marianum Extracts on the Acute Peritonitis Mouse Model

Journal of Arak University of Medical Sciences ◽

10.32598/jams.24.3.6154.1 ◽

2021 ◽

Vol 24 (3) ◽

pp. 372-385

Author(s):

Maryam Bahrami ◽

◽

Ali Ghazavi ◽

Ali Ganji ◽

Ghasem Mosayebi ◽

...

Keyword(s):

Acute Toxicity ◽

Therapeutic Potential ◽

Inflammatory Diseases ◽

Nigella Sativa ◽

Control Group ◽

Silybum Marianum ◽

Acute Peritonitis ◽

Anti Oxidant ◽

Anti Inflammatory ◽

Inflammatory Effect

Background and Aim: In addition to free radicals such as Nitric Oxide (NO), inflammation is one of the most important pathophysiological causes of peritonitis. Over thousands of years, Nigella Sativa (NS) and Silybum Marianum (SM) are two plants known for their anti-oxidant and anti-inflammatory properties. However, the effect of its compound is unclear. Thus, in this study, we evaluated the anti-inflammatory effect of NS and SM extracts and their combination on inflammatory diseases like thioglycollate peritoneal. Methods & Materials: Alcoholic extracts of SM and NS were obtained by the soxhlet method. Male Balb/C mice were divided into 5 groups and gavage orally for 14 days with SM, NS, the mixture of extracts of these two, DMSO 30% as the control group, and dexamethasone as the positive control group. The safety profile and acute toxicity in mice were assessed. On day 10, acute peritonitis was induced by thioglycollate 3%. Finally, the total anti-oxidant power and NO concentration were measured by FRAP and Griess method, respectively, in the serum of treated mice. Ethical Considerations: All experimental process was performed following the guidelines according to the Animal Ethics Committee of Arak University of Medical Sciences (IR.ARAKMU.REC.1397.359). Results: Acute toxicity test showed no significant changes in weight and physical appearance of the mice. However, the extract and their mixture decreased NO level significantly (P=0.000) in serum. Also, the mixture significantly increased total anti-oxidant power (P=0.015). Conclusion: Results showed that the SM and NS extract mixture demonstrated anti-inflammatory activity, inhibiting inflammatory mediators such as NO and increasing anti-oxidant power, thus supporting its therapeutic potential in slowing down inflammatory processes in inflammation disorders.

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IL-6, a Therapeutic Target and Omega-3 PUFA, a Host Modulator in Chronic Periodontitis

Biomedical & Pharmacology Journal ◽

10.13005/bpj/2332 ◽

2021 ◽

Vol 14 (4) ◽

pp. 2307-2318

Author(s):

Rajathilagam T Rajathilagam T ◽

Thuthi Mohan Thuthi Mohan ◽

Aruna B Patil ◽

Mohanavalli S Mohanavalli S ◽

Seethalakshmi S Seethalakshmi S

Keyword(s):

Immune Response ◽

Chronic Periodontitis ◽

Inflammatory Cytokine ◽

Inflammatory Diseases ◽

Omega 3 ◽

Tissue Destruction ◽

Open Label ◽

Pocket Depth ◽

Pufa Supplementation ◽

Anti Inflammatory

Periodontitis is a common multifactorial inflammatory disease with gradual loss of supportive tissues around the teeth which eventually leads to decrease in the quality of life. Blocking Interleukin-6 (IL-6), a multifunctional cytokine with pro-inflammatory properties has demonstrated therapeutic efficacy in inflammatory diseases like Rheumatoid arthritis, SLE and multiple sclerosis. Host immune response, the underlying cause for this progressive disease is targeted by Host modulatory therapy (HMT), an emerging treatment modality. Omega-3 polyunsaturated fatty acids (ώ 3 PUFAs), one of the relatively safe HMTs, reduces tissue destruction, stabilizes or even regenerates the periodontium through its anti-inflammatory & immunoregulatory properties. ώ 3 PUFAs are essential for the synthesis of eicosanoids which are involved in anti-inflammatory, antiplatelet aggregatory, vasodilation, vasoconstriction, immune response, cell growth and proliferation. The key factor examined and extrapolated in this study is the anti-inflammatory property of ώ 3 PUFA. The aim of the study was to evaluate the immunological and clinical response to ώ 3 PUFA supplementation therapy in chronic periodontitis by measuring the inflammatory cytokine, IL-6 levels in serum. In this open label exploratory study, 40 patients with a Female: Male ratio of 4:1were enrolled and assessed clinically by measuring Oral Hygiene Index-Simplified (OHI-S), Probing Pocket Depth (PPD), Clinical Attachment Level (CAL) and their serum for IL-6 levels. Subsequently 300 mg (concentration of EPA 180/DHA120) of ώ 3 PUFA was prescribed twice daily for 3 months and periodically reviewed to assess their IL-6 levels and periodontal status. IL-6 levels which were at a maximum mean of 10.2 pg/ml prior to treatment, showed a gradual and notable reduction to 2.3 pg/ml at the end of the study following ώ 3 PUFA supplementation therapy. The coefficient of variation R2 and ANOVA showed statistically significant periodic variation in biomarker IL-6 and in all clinical measurements at all time intervals. ώ 3 PUFA adjunctive therapy significantly reduces the inflammatory cytokine (IL-6) levels and causes noteworthy improvement of the most relevant clinical parameters (OHI-S, PPD, CAL). Hence ώ 3 PUFA can be recommended as a dietary supplementation and a safe host modulatory treatment in chronic periodontitis.

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CD169+ macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2108540119 ◽

2022 ◽

Vol 119 (3) ◽

pp. e2108540119

Author(s):

Abdouramane Camara ◽

Alice C. Lavanant ◽

Jun Abe ◽

Henri Lee Desforges ◽

Yannick O. Alexandre ◽

...

Keyword(s):

Immune Response ◽

Lymph Node ◽

Stromal Cells ◽

Marginal Zone ◽

Immune Defense ◽

Environmental Cues ◽

Macrophage Differentiation ◽

Reporter Mouse ◽

Cell Compartments ◽

Specific Identity

CD169+ macrophages reside in lymph node (LN) and spleen and play an important role in the immune defense against pathogens. As resident macrophages, they are responsive to environmental cues to shape their tissue-specific identity. We have previously shown that LN CD169+ macrophages require RANKL for formation of their niche and their differentiation. Here, we demonstrate that they are also dependent on direct lymphotoxin beta (LTβ) receptor (R) signaling. In the absence or the reduced expression of either RANK or LTβR, their differentiation is perturbed, generating myeloid cells expressing SIGN-R1 in LNs. Conditions of combined haploinsufficiencies of RANK and LTβR revealed that both receptors contribute equally to LN CD169+ macrophage differentiation. In the spleen, the Cd169-directed ablation of either receptor results in a selective loss of marginal metallophilic macrophages (MMMs). Using a RANKL reporter mouse, we identify splenic marginal zone stromal cells as a source of RANKL and demonstrate that it participates in MMM differentiation. The loss of MMMs had no effect on the splenic B cell compartments but compromised viral capture and the expansion of virus-specific CD8+ T cells. Taken together, the data provide evidence that CD169+ macrophage differentiation in LN and spleen requires dual signals from LTβR and RANK with implications for the immune response.

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Evaluation of antibody response to BNT162b2 mRNA COVID-19 vaccine in patients affected by immune-mediated inflammatory diseases up to 5 months after vaccination

Clinical and Experimental Medicine ◽

10.1007/s10238-021-00771-3 ◽

2021 ◽

Author(s):

Davide Firinu ◽

Andrea Perra ◽

Marcello Campagna ◽

Roberto Littera ◽

Giuseppe Fenu ◽

...

Keyword(s):

Immune Response ◽

Booster Dose ◽

Inflammatory Diseases ◽

Control Group ◽

Biological Drugs ◽

Humoral Immune ◽

Immune Mediated ◽

Significant Difference ◽

Anti Cd20 ◽

High Immunogenicity

AbstractSARS-CoV-2 vaccination with mRNA product BNT162b2 elicited high immunogenicity in healthy subjects in trials. This study aims to better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). We enrolled patients and healthy healthcare workers control group (HCW) that underwent mRNA BNT162b2 vaccination and measured the serum IgG anti-S-RBD response at booster dose (T1), one month after booster dose (T2) and up to 5 months (T3). Demographic, disease-specific and vaccination data were recorded. Vaccination response of 551 participants naïve to SARS-CoV-2 infection were included in HCW and 102 in the IMID group, analyzing separately those on anti-CD20. At T2 all naïve HCW developed anti-S-RBD-IgG, while 94% of IMID responded (p < 0.001). IMID patients had a significantly different level of IgG than HCW at both T1 (p = 0.031), T2 (p < 0.001), while there was no significant difference at T3. There were no statistically significant differences according to the IMID type or to ongoing treatment with immunosuppressants, corticosteroids or biological drugs other than anti-CD20. The proportion and magnitude of response was significantly lower in IMID treated with anti-CD20 drugs. There was a correlation with age at T1 and at T2 but not at T3, stronger in patients than in HCW. Immune response close after BNT162b2 vaccination is reduced in patients with IMID, but there is no significant difference at 5 months. The measured reduction is related to age and the disease itself rather than treatments, with the exception of anti-CD20 drugs.

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Immunomodulatory Role of Nutrients: How Can Pulmonary Dysfunctions Improve?

Frontiers in Nutrition ◽

10.3389/fnut.2021.674258 ◽

2021 ◽

Vol 8 ◽

Author(s):

Sarah Cristina Gozzi-Silva ◽

Franciane Mouradian Emidio Teixeira ◽

Alberto José da Silva Duarte ◽

Maria Notomi Sato ◽

Luana de Mendonça Oliveira

Keyword(s):

Fatty Acids ◽

Immune Response ◽

Immune System ◽

Viral Infections ◽

Inflammatory Diseases ◽

Dietary Factors ◽

Chronic Inflammatory Diseases ◽

Anti Inflammatory ◽

Lung Health

Nutrition is an important tool that can be used to modulate the immune response during infectious diseases. In addition, through diet, important substrates are acquired for the biosynthesis of regulatory molecules in the immune response, influencing the progression and treatment of chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). In this way, nutrition can promote lung health status. A range of nutrients, such as vitamins (A, C, D, and E), minerals (zinc, selenium, iron, and magnesium), flavonoids and fatty acids, play important roles in reducing the risk of pulmonary chronic diseases and viral infections. Through their antioxidant and anti-inflammatory effects, nutrients are associated with better lung function and a lower risk of complications since they can decrease the harmful effects from the immune system during the inflammatory response. In addition, bioactive compounds can even contribute to epigenetic changes, including histone deacetylase (HDAC) modifications that inhibit the transcription of proinflammatory cytokines, which can contribute to the maintenance of homeostasis in the context of infections and chronic inflammatory diseases. These nutrients also play an important role in activating immune responses against pathogens, which can help the immune system during infections. Here, we provide an updated overview of the roles played by dietary factors and how they can affect respiratory health. Therefore, we will show the anti-inflammatory role of flavonoids, fatty acids, vitamins and microbiota, important for the control of chronic inflammatory diseases and allergies, in addition to the antiviral role of vitamins, flavonoids, and minerals during pulmonary viral infections, addressing the mechanisms involved in each function. These mechanisms are interesting in the discussion of perspectives associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its pulmonary complications since patients with severe disease have vitamins deficiency, especially vitamin D. In addition, researches with the use of flavonoids have been shown to decrease viral replication in vitro. This way, a full understanding of dietary influences can improve the lung health of patients.

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