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

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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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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Analgesic and Anti-Inflammatory Activities of Methanol Extract ofFicus pumilaL. in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/340141 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Chi-Ren Liao ◽

Chun-Pin Kao ◽

Wen-Huang Peng ◽

Yuan-Shiun Chang ◽

Shang-Chih Lai ◽

...

Keyword(s):

Acetic Acid ◽

Methanol Extract ◽

Inflammatory Diseases ◽

Paw Edema ◽

Tissue Destruction ◽

Hplc Fingerprint ◽

Analgesic Effects ◽

Inflammatory Mechanism ◽

Tnf Α ◽

Anti Inflammatory

This study investigated possible analgesic and anti-inflammatory mechanisms of the methanol extract ofFicus pumila(FPMeOH). Analgesic effects were evaluated in two models including acetic acid-induced writhing response and formalin-induced paw licking. The results showedFPMeOHdecreased writhing response in the acetic acid assay and licking time in the formalin test. The anti-inflammatory effect was evaluated by λ-carrageenan-induced mouse paw edema and histopathological analyses.FPMeOHsignificantly decreased the volume of paw edema induced by λ-carrageenan. Histopathologically,FPMeOHabated the level of tissue destruction and swelling of the edema paws. This study indicated anti-inflammatory mechanism ofFPMeOHmay be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx, and GRd in the liver. Additionally,FPMeOHalso decreased the level of inflammatory mediators such as IL-1β, TNF-α, and COX-2. HPLC fingerprint was established and the contents of three active ingredients, rutin, luteolin, and apigenin, were quantitatively determined. This study provided evidence for the classical treatment ofFicus pumilain inflammatory diseases.

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Periodontal disease in patients with ankylosing spondylitis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2008.097212 ◽

2009 ◽

Vol 69 (01) ◽

pp. 34-38 ◽

Cited By ~ 30

Author(s):

N Pischon ◽

T Pischon ◽

E Gülmez ◽

J Kröger ◽

P Purucker ◽

...

Keyword(s):

New York ◽

Ankylosing Spondylitis ◽

Alcohol Consumption ◽

Periodontal Disease ◽

Inflammatory Diseases ◽

Stepwise Logistic Regression ◽

Tissue Destruction ◽

Pocket Depth ◽

Clinical Attachment Loss ◽

Attachment Loss

Objective:Ankylosing spondylitis (AS) and periodontal disease (PD) are characterised by dysregulation of the host inflammatory response, resulting in soft and hard connective tissue destruction. AS has been related to other inflammatory diseases, however, there is a paucity of data on whether AS is associated with inflammatory PD.Methods:The association between AS and PD was examined in 48 patients with AS and 48 healthy controls, matched for age and gender. AS was diagnosed according to the modified New York criteria. Periodontal examination included probing pocket depth (PPD), clinical attachment loss (CAL), plaque index (PI) and bleeding on probing (BOP). Potential risk factors of PD such as smoking, low education, alcohol consumption, body mass index (BMI), as well as chronic diseases associated with PD and AS were assessed through questionnaires.Results:In stepwise logistic regression, including AS status, age, gender, education, smoking, alcohol consumption and BMI, only AS status, age and education remained significant predictors of PD. Patients with AS had significant 6.81-fold increased odds (95% CI 1.96 to 23.67) of PD (defined as mean attachment loss >3 mm) compared to controls. The strength of the association was attenuated but remained statistically significant after further adjustment for plaque accumulation (odds ratio (OR) 5.48, 95% CI 1.37 to 22.00).Conclusions:The present study shows that patients with AS have a significantly higher risk of PD, strongly suggesting the need for close collaboration between rheumatologists, periodontists and dental hygienists when treating patients with AS.

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Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are key features of alpacas resolving MERS-CoV infection

10.1101/2020.11.23.395301 ◽

2020 ◽

Author(s):

Nigeer Te ◽

Jordi Rodon ◽

Maria Ballester ◽

Mónica Pérez ◽

Lola Pailler-García ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Nasal Mucosa ◽

Inflammatory Cytokine ◽

Innate Immune ◽

Type I ◽

Innate Immune Responses ◽

Interferon Stimulated Genes ◽

Anti Inflammatory ◽

Anti Inflammatory Cytokine

ABSTRACTWhile MERS-CoV (Middle East respiratory syndrome Coronavirus) provokes a lethal disease in humans, camelids, the main virus reservoir, are asymptomatic carriers, suggesting a crucial role for innate immune responses in controlling the infection. Experimentally infected camelids clear infectious virus within one week and mount an effective adaptive immune response. Here, transcription of immune response genes was monitored in the respiratory tract of MERS-CoV infected alpacas. Concomitant to the peak of infection, occurring at 2 days post inoculation (dpi), type I and III interferons (IFNs) were maximally transcribed only in the nasal mucosa of alpacas, provoking the induction of interferon stimulated genes (ISGs) along the whole respiratory tract. Simultaneous to mild focal infiltration of leukocytes in nasal mucosa and submucosa, upregulation of the anti-inflammatory cytokine IL10 and dampened transcription of pro-inflammatory genes under NF-κB control were observed. In the lung, early (1 dpi) transcription of chemokines (CCL2 and CCL3) correlated with a transient accumulation of mainly mononuclear leukocytes. A tight regulation of IFNs in lungs with expression of ISGs and controlled inflammatory responses, might contribute to virus clearance without causing tissue damage. Thus, the nasal mucosa, the main target of MERS-CoV in camelids, is central in driving an efficient innate immune response based on triggering ISGs as well as the dual anti-inflammatory effects of type III IFNs and IL10.IMPORTANCEMiddle East respiratory syndrome coronavirus (MERS-CoV) is the etiological agent of a respiratory disease causing high mortality in humans. In camelids, the main MERS-CoV reservoir host, viral infection leads to subclinical disease. Our study describes transcriptional regulations of innate immunological pathways underlying asymptomatic clinical manifestations of alpacas in response to MERS-CoV. Concomitant to the peak of infection, these animals elicited a strong transient interferon response and induction of the anti-inflammatory cytokine IL10 in the nasal mucosa. This was associated to a dimmed regulation of pro-inflammatory cytokines and induction of interferon stimulated genes along the whole respiratory mucosa, leading to the rapid clearance of the virus. Thus, innate immune responses occurring in the nasal mucosa appear to be the key in controlling MERS-CoV disease by avoiding a cytokine storm. Understanding on how asymptomatic host reservoirs counteract MERS-CoV infection will aid in the development of antiviral drugs and vaccines.

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Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are key features of alpacas resolving MERS-CoV infection

10.1101/2020.12.22.423939 ◽

2020 ◽

Author(s):

Nigeer Te ◽

Jordi Rodon ◽

Maria Ballester ◽

Mónica Pérez ◽

Lola Pailler-García ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Nasal Mucosa ◽

Inflammatory Cytokine ◽

Innate Immune ◽

Type I ◽

Innate Immune Responses ◽

Interferon Stimulated Genes ◽

Anti Inflammatory ◽

Anti Inflammatory Cytokine

AbstractWhile MERS-CoV (Middle East respiratory syndrome Coronavirus) provokes a lethal disease in humans, camelids, the main virus reservoir, are asymptomatic carriers, suggesting a crucial role for innate immune responses in controlling the infection. Experimentally infected camelids clear infectious virus within one week and mount an effective adaptive immune response. Here, transcription of immune response genes was monitored in the respiratory tract of MERS-CoV infected alpacas. Concomitant to the peak of infection, occurring at 2 days post inoculation (dpi), type I and III interferons (IFNs) were maximally transcribed only in the nasal mucosa of alpacas, provoking the induction of interferon stimulated genes (ISGs) along the whole respiratory tract. Simultaneous to mild focal infiltration of leukocytes in nasal mucosa and submucosa, upregulation of the anti-inflammatory cytokine IL10 and dampened transcription of pro-inflammatory genes under NF-κB control were observed. In the lung, early (1 dpi) transcription of chemokines (CCL2 and CCL3) correlated with a transient accumulation of mainly mononuclear leukocytes. A tight regulation of IFNs in lungs with expression of ISGs and controlled inflammatory responses, might contribute to virus clearance without causing tissue damage. Thus, the nasal mucosa, the main target of MERS-CoV in camelids, is central in driving an efficient innate immune response based on triggering ISGs as well as the dual anti-inflammatory effects of type III IFNs and IL10.Author summaryMiddle East respiratory syndrome coronavirus (MERS-CoV) is the etiological agent of a respiratory disease causing high mortality in humans. In camelids, the main MERS-CoV reservoir host, viral infection leads to subclinical disease. Our study describes transcriptional regulations of innate immunological pathways underlying asymptomatic clinical manifestations of alpacas in response to MERS-CoV. Concomitant to the peak of infection, these animals elicited a strong transient interferon response and induction of the anti-inflammatory cytokine IL10 in the nasal mucosa. This was associated to a dimmed regulation of pro-inflammatory cytokines and induction of interferon stimulated genes along the whole respiratory mucosa, leading to the rapid clearance of the virus. Thus, innate immune responses occurring in the nasal mucosa appear to be the key in controlling MERS-CoV disease by avoiding a cytokine storm. Understanding on how asymptomatic host reservoirs counteract MERS-CoV infection will aid in the development of antiviral drugs and vaccines.

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IFN-τDisplays Anti-Inflammatory Effects onStaphylococcus aureusEndometritis via Inhibiting the Activation of the NF-κB and MAPK Pathways in Mice

BioMed Research International ◽

10.1155/2017/2350482 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12

Author(s):

Zhenbiao Zhang ◽

Yingfang Guo ◽

Yuzhu Liu ◽

Chengye Li ◽

Mengyao Guo ◽

...

Keyword(s):

Mouse Model ◽

Protective Effect ◽

Inflammatory Cytokine ◽

Inflammatory Diseases ◽

Potential Drug ◽

Histopathological Changes ◽

Uterine Infection ◽

Anti Inflammatory ◽

Anti Inflammatory Cytokine ◽

Inflammatory Effect

The aim of the present study was to determine the anti-inflammatory effect of IFN-τon endometritis using a mouse model ofS. aureus-induced endometritis and to elucidate the mechanism of action underlying these effects. In the present study, the effect of IFN-τonS. aureusgrowth was monitored by turbidimeter at 600 nm. IFN-τdid not affectS. aureusgrowth. The histopathological changes indicated that IFN-τhad a protective effect on uterus tissues withS. aureusinfection. The ELISA and qPCR results showed the production of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 was decreased with IFN-τtreatment. In contrast, the level of the anti-inflammatory cytokine IL-10 was increased. We further studied the signaling pathway associated with these observations, and the qPCR results showed that the expression of TLR2 was repressed by IFN-τ. Furthermore, the western blotting results showed the phosphorylation of IκB, NF-κB p65, and MAPKs (p38, JNK, and ERK) was inhibited by IFN-τtreatment. The results suggested that IFN-τmay be a potential drug for the treatment of uterine infection due toS. aureusor other infectious inflammatory diseases.

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Effect of omega-3 supplementation on neuropathy in type 1 diabetes

Neurology ◽

10.1212/wnl.0000000000004033 ◽

2017 ◽

Vol 88 (24) ◽

pp. 2294-2301 ◽

Cited By ~ 29

Author(s):

Evan J.H. Lewis ◽

Bruce A. Perkins ◽

Leif E. Lovblom ◽

Richard P. Bazinet ◽

Thomas M.S. Wolever ◽

...

Keyword(s):

Type 1 Diabetes ◽

Nerve Conduction ◽

Sensory Function ◽

Omega 3 ◽

Open Label ◽

Pufa Supplementation ◽

Corneal Confocal Microscopy ◽

Seal Oil

Objective:To test the hypothesis that 12 months of seal oil omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation will stop the known progression of diabetic sensorimotor polyneuropathy (DSP) in type 1 diabetes mellitus (T1DM).Methods:Individuals with T1DM and evidence of DSP as determined by a Toronto Clinical Neuropathy Score ≥1 were recruited to participate in a single-arm, open-label trial of seal oil ω-3 PUFA supplementation (10 mL·d−1; 750 mg eicosapentaenoic acid, 560 mg docosapentaenoic acid, and 1,020 mg docosahexaenoic acid) for 1 year. The primary outcome was the 1-year change in corneal nerve fiber length (CNFL) measured by in vivo corneal confocal microscopy, with sensory and nerve conduction measures as secondary outcomes.Results:Forty participants (53% female), aged 48 ± 14 years, body mass index 28.1 ± 5.8 with diabetes duration of 27 ± 18 years, were enrolled. At baseline, 23 participants had clinical DSP and 17 did not. Baseline CNFL was 8.3 ± 2.9 mm/mm2 and increased 29% to 10.1 ± 3.7 mm/mm2 (p = 0.002) after 12 months of supplementation. There was no change in nerve conduction or sensory function.Conclusions:Twelve months of ω-3 supplementation was associated with increase in CNFL in T1DM.ClinicalTrials.govidentifier:NCT02034266.Classification of evidence:This study provides Class IV evidence that for patients with T1DM and evidence of DSP, 12 months of seal oil omega-3 supplementation increases CNFL.

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Omega-3 Polyunsaturated Fatty Acids in Physical Performance Optimization

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.23.1.83 ◽

2013 ◽

Vol 23 (1) ◽

pp. 83-96 ◽

Cited By ~ 48

Author(s):

Timothy D. Mickleborough

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Exercise Performance ◽

Performance Optimization ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Omega 3 ◽

Cell Deformability ◽

Pufa Supplementation ◽

The Impact

Increased muscle oxidative stress and inflammatory responses among athletes have been reported consistently. In addition, it is well known that exhaustive or unaccustomed exercise can lead to muscle fatigue, delayed-onset muscle soreness, and a decrement in performance. Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to decrease the production of inflammatory eicosanoids, cytokines, and reactive oxygen species; have immunomodulatory effects; and attenuate inflammatory diseases. While a number of studies have assessed the efficacy of omega-3 PUFA supplementation on red blood cell deformability, muscle damage, inflammation, and metabolism during exercise, only a few have evaluated the impact of omega-3 PUFA supplementation on exercise performance. It has been suggested that the ingestion of EPA and DHA of approximately 1–2 g/d, at a ratio of EPA to DHA of 2:1, may be beneficial in counteracting exercise-induced inflammation and for the overall athlete health. However, the human data are inconclusive as to whether omega-3 PUFA supplementation at this dosage is effective in attenuating the inflammatory and immunomodulatory response to exercise and improving exercise performance. Thus, attempts should be made to establish an optimal omega-3 fatty-acid dosage to maximize the risk-to-reward ratio of supplementation. It should be noted that high omega-3 PUFA consumption may lead to immunosuppression and prolong bleeding time. Future studies investigating the efficacy of omega-3 PUFA supplementation in exercise-trained individuals should consider using an exercise protocol of sufficient duration and intensity to produce a more robust oxidative and inflammatory response.

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Omega 3 Fatty Acid and Skin Diseases

Frontiers in Immunology ◽

10.3389/fimmu.2020.623052 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yu Sawada ◽

Natsuko Saito-Sasaki ◽

Motonobu Nakamura

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Food Intake ◽

Skin Diseases ◽

Inflammatory Diseases ◽

Influential Factors ◽

Omega 3 ◽

Omega 3 Fatty Acid ◽

Beneficial Effects ◽

Anti Inflammatory

Humans are exposed to various external environmental factors. Food intake is one of the most influential factors impacting daily lifestyle. Among nutrients obtained from foods, omega-3 polyunsaturated fatty acids (PUFAs) have various beneficial effects on inflammatory diseases. Furthermore, omega-3 PUFA metabolites, including resolvins, are known to demonstrate strong anti-inflammatory effects during allergic and inflammatory diseases; however, little is known regarding the actual impact of these metabolites on skin diseases. In this review, we focused on metabolites that have strong anti-inflammatory actions in various inflammatory diseases, as well as those that present antitumor actions in malignancies, in addition to the actual effect of omega-3 PUFA metabolites on various cells.

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An impact of the combined drug containing antimicrobial, antiprotozoal, antifungal and glucocorticoid agents on local immunity in women with bacterial vaginosis and non-specific vaginitis

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-aio-1462 ◽

2021 ◽

Vol 11 (3) ◽

pp. 549-555

Author(s):

O. M. Bokach ◽

M. S. Murasheva ◽

M. S. Selkova ◽

K. V. Storozheva ◽

S. V. Chepanov ◽

...

Keyword(s):

Bacterial Vaginosis ◽

Inflammatory Cytokine ◽

Randomized Clinical Trials ◽

Inflammatory Diseases ◽

Vaginal Mucosa ◽

Vaginal Smears ◽

Local Immunity ◽

Therapeutic Concept ◽

Frequent Relapses ◽

Anti Inflammatory

Inflammatory diseases of the vagina related to imbalanced microflora composition represent one of the most common gynecological diseases primarily dealt with by obstetrician/gynecologists. Such diseases markedly worsen female patient quality of life as well as affect female reproductive system resulting both in altered fertility and adverse pregnancy outcomes. By now, multiple therapeutic and preventive protocols have been proposed to manage such diseases, but insufficient therapeutic efficacy and frequent relapses require further investigations. The aim of the study was to evaluate an effect of the drug Elgyna (Wertex, Russia) consisting of antibacterial, antifungal and glucocorticoid agents on local immunity in females with bacterial vaginosis and nonspecific vaginitis. For this, there were examined and treated 24 females enrolled to the study, who underwent gynecological examination (speculum and bimanual vaginal examination), cervical epithelium microscopy, and calculating karyopicnotic index. Special attention was paid to quantifying level of cytokines IL-6, IL-10, TNFα in vaginal smears before and after therapy with the drug Elgyna. It was found that by the end of the therapy course vaginally administered Elgyna resulted in significantly ameliorated clinical symptoms and normalized microscopic parameters of vaginal discharge. Moreover, this drug consisting of antibacterial, antifungal and glucocorticoid agents did not suppress vaginal epithelium proliferation, but lowered production of pro-inflammatory cytokine TNFα in vaginal smears and shifted toward anti-inflammatory cytokine production. This evidence pathogenetically justifies administration of the drug Elgyna in females with bacterial vaginosis and nonspecific vaginitis as an anti-inflammatory medicine. Efficacy and safety of the two-step therapeutic approach consisting of antibacterial therapy followed by vaginal microbiota recovery for treating inflammatory diseases of vaginal mucosa were confirmed in multiple randomized clinical trials. We envision that such therapeutic concept might be added with a third component implying correction of local vaginal immunity aimed at normalizing the balance between pro- and anti-inflammatory cytokines.

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