Inflammation Abstracts 2

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The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease.
            (Barden et al., 2018)  Download
BACKGROUND:  Neutrophils release leukotriene (LT)B|4| and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB|5| and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB|4|. OBJECTIVE:  This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD. DESIGN:  In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks. RESULTS:  Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB|5| (P < 0.0001) and the SPM 18-hydroxyeicosapentaenoic acid (18-HEPE), resolvin E1 (RvE1), resolvin E2 (RvE2) and resolvin E3 (RvE3) that derive from EPA, as well as 17-hydroxydocosahexaenoic acid (17-HDHA) and resolvin D5 (RvD5) that derive from DHA (all P < 0.01). Neutrophil LTB4 and its metabolites, and 5-HETE were not significantly altered by n-3 FA or CoQ. Plasma MPO was significantly reduced with n-3 FA alone (P = 0.013) but not when given in combination with CoQ. CONCLUSION:  n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB|5| and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation.

Pro-resolving lipid mediators: Agents of anti-ageing
            (Doyle et al., 2018)  Download
Inflammation is an essential response to injury and its timely and adequate resolution permits tissue repair and avoidance of chronic inflammation. Ageing is associated with increased inflammation, sub-optimal resolution and these act as drivers for a number of ageing-associated pathologies. We describe the role played by specialised proresolving lipid mediators (SPMs) in the resolution of inflammation and how insufficient levels of these mediators, or compromised responsiveness may play a role in the pathogenesis of many ageing-associated pathologies, e.g. Alzheimer's Disease, atherosclerosis, obesity, diabetes and kidney disease. Detailed examination of the resolution phase of inflammation highlights the potential to harness these lipid mediators and or mimetics of their bioactions, in particular, their synthetic analogues to promote effective resolution of inflammation, without compromising the host immune system.

Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo.
            (Hasturk et al., 2007)  Download
Resolvin E1 (RvE1) is a potent proresolving mediator of inflammation derived from omega-3 eicosapentaenoic acid that acts locally to stop leukocyte recruitment and promote resolution. RvE1 displays potent counter-regulatory and tissue-protective actions in vitro and in vivo. Periodontal disease is a local inflammatory disease initiated by bacteria characterized by neutrophil-mediated tissue injury followed by development of a chronic immune lesion. In this study, we report the treatment of established periodontitis using RvE1 as a monotherapy in rabbits compared with structurally related lipids PGE(2) and leukotriene B(4). PGE(2) and leukotriene B(4) each enhanced development of periodontitis and worsened the severity of disease. Promotion of resolution of inflammation as a therapeutic target with RvE1 resulted in complete restoration of the local lesion, and reduction in the systemic inflammatory markers C-reactive protein and IL-1beta. This report is the first to show that resolution of inflammation by a naturally occurring endogenous lipid mediator results in complete regeneration of pathologically lost tissues, including bone.

What is the impact of n-3 PUFAs on inflammation markers in Type 2 diabetic mellitus populations?: a systematic review and meta-analysis of randomized controlled trials.
            (Lin et al., 2016)  Download
OBJECTIVES:  To explore the possible role of n-3 polyunsaturated fatty acids (PUFAs) in lowering inflammation markers in individuals with type 2 diabetes mellitus. METHODS:  PubMed, CNKI and Cochrane databases were searched until December 30, 2015; references from papers or reviews were also retrieved and screened. Screening was performed by two independent researchers, and randomized controlled trials reporting the specific n-3 PUFA type, dose, frequency, and duration of treatment, as well as the baseline and follow-up concentrations of inflammation markers, including interleukin 2 (IL-2), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and C-reactive protein (CRP), were selected for final analysis. Data analysis was performed using RevMan 5.2 software. RESULTS:  Eight studies involving 955 participants were included; all reported CRP. Only one included study reported IL-2 or IL-6 while two studies reported TNF-α. N-3 PUFAs significantly reduced CRP concentration compared with control [SMD 95 % CI, 1.90 (0.64, 3.16), Z = 2.96, P = 0.003, random effect model]. CONCLUSIONS:  N-3 PUFAs decrease CRP concentration in type-2 diabetes mellitus. However, larger and rigorously designed RCTs are required to confirm this finding and extend it into other inflammatory biomarkers.


Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans.
            (Navarro et al., 2015)  Download
BACKGROUND:  Glucosamine and chondroitin are popular non-vitamin dietary supplements used for osteoarthritis. Long-term use is associated with lower incidence of colorectal and lung cancers and with lower mortality; however, the mechanism underlying these observations is unknown. In vitro and animal studies show that glucosamine and chondroitin inhibit NF-kB, a central mediator of inflammation, but no definitive trials have been done in healthy humans. METHODS:  We conducted a randomized, double-blind, placebo-controlled, cross-over study to assess the effects of glucosamine hydrochloride (1500 mg/d) plus chondroitin sulfate (1200 mg/d) for 28 days compared to placebo in 18 (9 men, 9 women) healthy, overweight (body mass index 25.0-32.5 kg/m2) adults, aged 20-55 y. We examined 4 serum inflammatory biomarkers: C-reactive protein (CRP), interleukin 6, and soluble tumor necrosis factor receptors I and II; a urinary inflammation biomarker: prostaglandin E2-metabolite; and a urinary oxidative stress biomarker: F2-isoprostane. Plasma proteomics on an antibody array was performed to explore other pathways modulated by glucosamine and chondroitin. RESULTS:  Serum CRP concentrations were 23% lower after glucosamine and chondroitin compared to placebo (P = 0.048). There were no significant differences in other biomarkers. In the proteomics analyses, several pathways were significantly different between the interventions after Bonferroni correction, the most significant being a reduction in the "cytokine activity" pathway (P = 2.6 x 10-16), after glucosamine and chondroitin compared to placebo. CONCLUSION:  Glucosamine and chondroitin supplementation may lower systemic inflammation and alter other pathways in healthy, overweight individuals. This study adds evidence for potential mechanisms supporting epidemiologic findings that glucosamine and chondroitin are associated with reduced risk of lung and colorectal cancer. TRIAL REGISTRATION:  ClinicalTrials.gov NCT01682694.

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.
            (Ridker et al., 2017) Download
BACKGROUND:  Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS:  We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS:  At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS:  Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846 .).

Amino acid supplementation is anabolic during the acute phase of endotoxin-induced inflammation: A human randomized crossover trial.
            (Rittig et al., 2016)  Download
BACKGROUND & AIMS:  Inflammation is catabolic and causes muscle loss. It is unknown if amino acid supplementation reverses these effects during the acute phase of inflammation. The aim was to test whether amino acid supplementation counteracts endotoxin-induced catabolism. METHODS:  Eight young, healthy, lean males were investigated three times in randomized order: (i) normal conditions (Placebo), (ii) endotoxemia (LPS), and (iii) endotoxemia with amino acid supplementation (LPS + A). Protein kinetics were determined using phenylalanine, tyrosine, and urea tracers. Each study day consisted of a four-hour non-insulin stimulated period and a two-hour hyperinsulinemic euglycemic clamp period. Muscle biopsies were collected once each period. RESULTS:  Endotoxin administration created a significant inflammatory response (cytokines, hormones, and vital parameters) without significant differences between LPS and LPS + A. Whole body protein breakdown was elevated during LPS compared with Placebo and LPS + A (p < 0.05). Whole body protein synthesis was higher during LPS + A than both Placebo and LPS (p < 0.003). Furthermore, protein synthesis was higher during LPS than during Placebo (p < 0.02). Net muscle phenylalanine release was markedly decreased during LPS + A (p < 0.004), even though muscle protein synthesis and breakdown rates did not differ significantly between interventions. LPS + A increased mammalian target of rapamycin (mTOR) phosphorylation (p < 0.05) and eukaryotic translation factor 4E-binding protein 1 (4EBP1) phosphorylation (p = 0.007) without activating AMPK or affecting insulin signaling through Akt. During insulin stimulation net muscle phenylalanine release and protein degradation were further reduced. CONCLUSIONS:  Amino acid supplementation in the acute phase of inflammation reduces whole body and muscle protein loss, and this effect is associated with activation of mTOR and downstream signaling to protein synthesis through mTORC1, suggesting a therapeutic role for intravenous amino acids in inflammatory states. CLINICAL TRIAL REGISTRY:  The Central Denmark Region Ethics Commitee (1-10-71-410-12) www.clinicaltrials.gov (identification number NCT01705782).

Supplementation with selenium and human immune cell functions. I. Effect on lymphocyte proliferation and interleukin 2 receptor expression.
            (Roy et al., 1994)   Download
Selenium (Se) is an essential nutritional factor that was shown by us to alter the expression of the high affinity interleukin 2 receptor (Il2-R) and its subunits, cell proliferation, and clonal expansion of cytotoxic T-lymphocytes in mice. This study shows that dietary supplementation of Se-replete humans with 200 micrograms/d of sodium selenite for 8 wk, or in vitro supplementation with 1 x 10(-7) M Se (as sodium selenite), result in a significant augmentation of the ability of peripheral blood lymphocytes to respond to stimulation with 1 microgram/mL of phytohemagglutinin or alloantigen (mixed lymphocyte reaction) and to express high affinity Il2-R on their surface. There was a clear correlation between supplementation with Se and enhanced 3H-thymidine incorporation into nuclear DNA, preceded by enhanced expression of high affinity Il2-R. Supplementation with Se can apparently modulate T-lymphocyte mediated immune responses in humans that depend on signals generated by the interaction of interleukin 2 with Il2-R.

Oral Vitamin D Rapidly Attenuates Inflammation from Sunburn: An Interventional Study.
            (Scott et al., 2017)  Download
The diverse immunomodulatory effects of vitamin D are increasingly being recognized. However, the ability of oral vitamin D to modulate acute inflammation in vivo has not been established in humans. In a double-blinded, placebo-controlled interventional trial, 20 healthy adults were randomized to receive either placebo or a high dose of vitamin D|3| (cholecalciferol) one hour after experimental sunburn induced by an erythemogenic dose of UVR. Compared with placebo, participants receiving vitamin D|3| (200,000 international units) demonstrated reduced expression of proinflammatory mediators tumor necrosis factor-α (P = 0.04) and inducible nitric oxide synthase (P = 0.02) in skin biopsy specimens 48 hours after experimental sunburn. A blinded, unsupervised hierarchical clustering of participants based on global gene expression profiles revealed that participants with significantly higher serum vitamin D|3| levels after treatment (P = 0.007) demonstrated increased skin expression of the anti-inflammatory mediator arginase-1 (P = 0.005), and a sustained reduction in skin redness (P = 0.02), correlating with significant expression of genes related to skin barrier repair. In contrast, participants with lower serum vitamin D|3| levels had significant expression of proinflammatory genes. Together the data may have broad implications for the immunotherapeutic properties of vitamin D in skin homeostasis, and implicate arginase-1 upregulation as a previously unreported mechanism by which vitamin D exerts anti-inflammatory effects in humans.


 

Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and pharmacology.
            (Serhan, 2017)  Download
It is with great pleasure that I write this foreword and introduction to this Special Issue dedicated to the protective actions of the pro-resolving mediators and edited by my colleague Dr. Jesmond Dalli. Many of my collaborators and colleagues that helped to uncover the actions and clinical potential of the resolvins and other specialized proresolving mediators (SPM), namely, the superfamily of pro-resolving mediators that includes the resolvin (E-series, D-series and DPA-derived), protectin and maresin families, as well as the arachidonic acid-derived lipoxins, join me in this special issue. They have given contributions that present exciting new results on the remarkable actions and potency of these unique molecules, the SPM moving forward the importance of their mediators and pathways in human biology. Each contribution to this issue is presented by world authorities in their respective fields covering discoveries that demonstrate the importance and impact of resolution mediators in biology, medicine and surgery. While some of the authors were students and/or fellows with me and others, they are today the founding "resolutionists" of a new era of appreciation of autacoid biosynthesis and metabolomics in human health and disease with their rigorous attention to experimental detail and discovery. The chapters of this issue are filled with exciting new discoveries demonstrating the dynamics and potential of resolution mediators.

Raw and Red-Hot: Could inflammation be the cause of myriad chronic conditions
            (Shaw, 2019)  Download
We were actually surprised that reduced inflammation was the biggest explainer, the biggest contributor to the benefit of activity,” says Mora, “because we hadn’t hypothesized that. We knew that regular exercise does reduce inflammation over the long term, but we also knew that acute exercise transiently increases inflammatory biomarkers during and immediately after exertion.” About a third of the benefit of regular exercise, they found, is attributable to reduced inflammation. The anti-inflammatory effect of exercise was much greater than most people had expected. That raised another question: whether inflammation might also play a dominant role in other lifestyle illnesses that have been linked to cardiovascular disease, such as diabetes and dementia.

Resolvin D2 Induces Resolution of Periapical Inflammation and Promotes Healing of Periapical Lesions in Rat Periapical Periodontitis.
            (Siddiqui et al., 2019)  Download
Periapical periodontitis results from pulpal infection leading to pulpal necrosis and resorption of periapical bone. The current treatment is root canal therapy, which attempts to eliminate infection and necrotic tissue. But, in some cases periapical inflammation doesn't resolve even after treatment. Resolvins belongs to a large family of specialized pro-resolving lipid mediators that actively resolves inflammation signaling via specific receptors. Resolvin D2 (RvD2), a metabolite of docosahexaenoic acid (DHA), was tested as an intracanal medicament in rats in vivo. Mechanism was evaluated in rat primary dental pulp cells (DPCs) in vitro. The results demonstrate that RvD2 reduces inflammatory cell infiltrate, periapical lesion size, and fosters pulp like tissue regeneration and healing of periapical lesion. RvD2 enhanced expression of its receptor, GPR18, dentin matrix acidic phosphoprotein 1 (DMP1) and mineralization in vivo and in vitro. Moreover, RvD2 induces phosphorylation of Stat3 transcription factor in dental pulp cells. We conclude that intracanal treatment with RvD2 resolves inflammation and promoting calcification around root apex and healing of periapical bone lesions. The data suggest that RvD2 induces active resolution of inflammation with pulp-like tissue regeneration after root canal infection and thus maybe suitable for treating periapical lesions.

High Dose Supplementation of Vitamin D Affects Measures of Systemic Inflammation: Reductions in High Sensitivity C-Reactive Protein Level and Neutrophil to Lymphocyte Ratio (NLR) Distribution.
            (Tabatabaeizadeh et al., 2017)  Download
The prevalence of Vitamin D deficiency is increasing worldwide, which has be shown to be associated with increased risk of cardiovascular disease (CVD), autoimmune disease, and metabolic syndrome. These conditions are also associated with a heightened state of inflammation. The aim of the current study was to evaluate the effect of vitamin D supplementation on serum C-Reactive Protein (CRP) level and Neutrophil-to-lymphocyte ratio (NLR) distribution in a large cohort of adolescent girls. A total of 580 adolescent girls were recruited follow by evaluation of CRP and hematological parameters before and after supplementation with vitamin D supplements as 9 of 50000 IU cholecalciferol capsules for 9 weeks taken at weekly intervals. At baseline, serum hs-CRP level was 0.9 (95%CI: 0.5-1.8), while this value after intervention was reduced to 0.8 (95%CI: 0.3-1.6; P = 0.007). Similar results were also detected for NLR (e.g., NLR level was 1.66 ± 0.72 and 1.53 ± 0.67, P = 0.002, before and after therapy with compliance rate of >95.2%). Moreover, we found an association between hs-CRP and BMI, triglyceride, white blood cell count, and lymphocytes. Interestingly we observed a significant reduction in neutrophil count and CRP level after high dose vitamin D supplementation. Our findings showed that the high dose supplementation of vitamin D affects measures of systemic inflammation: reductions in High Sensitivity C-Reactive Protein level and Neutrophil-to-lymphocyte ratio (NLR) distribution. J. Cell. Biochem. 118: 4317-4322, 2017. © 2017 Wiley Periodicals, Inc.

The effects of curcumin-containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials.
            (Tabrizi et al., 2019)  Download
Besides other benefits, curcumin is getting more recognized for its antioxidant and anti-inflammatory properties, highlighting the importance of curcumin application for chronic disease prevention. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the influence of curcumin-containing supplements on biomarkers of inflammation and oxidative stress. MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched till January 2018 for eligible studies. The selected studies were evaluated for their quality using the Cochrane risk of bias tool and relevant data were extracted from included studies. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Fifteen RCTs were included in the final analysis. The meta-analysis indicated that curcumin supplementation significantly decreased interleukin 6 (IL-6) (SMD -2.08; 95% CI [-3.90, -0.25]; p = 0.02), high-sensitivity C-reactive protein (hs-CRP) (SMD -0.65; 95% CI [-1.20, -0.10], p = 0.02), and malondialdehyde (MDA) concentrations (SMD -3.14; 95% CI [-4.76, -1.53], p < 0.001). Though, curcumin supplementation had no significant effect on tumor necrosis factor-alpha (SMD -1.62; 95% CI [-3.60, 0.36]; p = 0.10) and superoxide dismutase levels (SMD 0.34; 95% CI [-1.06, 1.74], p = 0.63). Overall, this meta-analysis suggests that taking curcumin-containing supplements may exert anti-inflammatory and antioxidant properties through a significant reduction in IL-6, hs-CRP, and MDA levels.

Suppressed liver tumorigenesis in fat-1 mice with elevated omega-3 fatty acids is associated with increased omega-3 derived lipid mediators and reduced TNF-α.
            (Weylandt et al., 2011)  Download
Liver tumors, particularly hepatocellular carcinoma (HCC), are a major cause of morbidity and mortality worldwide. The development of HCC is mostly associated with chronic inflammatory liver disease of various etiologies. Previous studies have shown that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) dampen inflammation in the liver and decrease formation of tumor necrosis factor (TNF)-α. In this study, we used the fat-1 transgenic mouse model, which endogenously forms n-3 PUFA from n-6 PUFA to determine the effect of an increased n-3 PUFA tissue status on tumor formation in the diethylnitrosamine (DEN)-induced liver tumor model. Our results showed a decrease in tumor formation, in terms of size and number, in fat-1 mice compared with wild-type littermates. Plasma TNF-α levels and liver cyclooxygenase-2 expression were markedly lower in fat-1 mice. Furthermore, there was a decreased fibrotic activity in the livers of fat-1 mice. Lipidomics analyses of lipid mediators revealed significantly increased levels of the n-3 PUFA-derived 18-hydroxyeicosapentaenoic acid (18-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDHA) in the livers of fat-1 animals treated with DEN. In vitro experiments showed that 18-HEPE and 17-HDHA could effectively suppress lipopolysacharide-triggered TNF-α formation in a murine macrophage cell line. The results of this study provide evidence that an increased tissue status of n-3 PUFA suppresses liver tumorigenesis, probably through inhibiting liver inflammation. The findings also point to a potential anticancer role for the n-3 PUFA-derived lipid mediators 18-HEPE and 17-HDHA, which can downregulate the important proinflammatory and proproliferative factor TNF-α.

 


References

Barden, AE, et al. (2018), ‘The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease.’, Prostaglandins Other Lipid Mediat, 136 1-8. PubMed: 29577973
Doyle, R, DM Sadlier, and C Godson (2018), ‘Pro-resolving lipid mediators: Agents of anti-ageing’, Semin Immunol, 40 36-48. PubMed: 30293857
Hasturk, H, et al. (2007), ‘Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo.’, J Immunol, 179 (10), 7021-29. PubMed: 17982093
Lin, N, et al. (2016), ‘What is the impact of n-3 PUFAs on inflammation markers in Type 2 diabetic mellitus populations?: a systematic review and meta-analysis of randomized controlled trials.’, Lipids Health Dis, 15 133. PubMed: 27544079
Navarro, SL, et al. (2015), ‘Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans.’, PLoS One, 10 (2), e0117534. PubMed: 25719429
Ridker, PM, et al. (2017), ‘Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.’, N Engl J Med, 377 (12), 1119-31. PubMed: 28845751
Rittig, N, et al. (2016), ‘Amino acid supplementation is anabolic during the acute phase of endotoxin-induced inflammation: A human randomized crossover trial.’, Clin Nutr, 35 (2), 322-30. PubMed: 25896101
Roy, M, et al. (1994), ‘Supplementation with selenium and human immune cell functions. I. Effect on lymphocyte proliferation and interleukin 2 receptor expression.’, Biol Trace Elem Res, 41 (1-2), 103-14. PubMed: 7946898
Scott, JF, et al. (2017), ‘Oral Vitamin D Rapidly Attenuates Inflammation from Sunburn: An Interventional Study.’, J Invest Dermatol, 137 (10), 2078-86. PubMed: 28576736
Serhan, CN (2017), ‘Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and pharmacology.’, Mol Aspects Med, 58 1-11. PubMed: 28263773
Shaw, J (2019), ‘Raw and Red-Hot: Could inflammation be the cause of myriad chronic conditions’, Harvard Magazine, PubMed:
Siddiqui, YD, et al. (2019), ‘Resolvin D2 Induces Resolution of Periapical Inflammation and Promotes Healing of Periapical Lesions in Rat Periapical Periodontitis.’, Front Immunol, 10 307. PubMed: 30863409
Tabatabaeizadeh, SA, et al. (2017), ‘High Dose Supplementation of Vitamin D Affects Measures of Systemic Inflammation: Reductions in High Sensitivity C-Reactive Protein Level and Neutrophil to Lymphocyte Ratio (NLR) Distribution.’, J Cell Biochem, 118 (12), 4317-22. PubMed: 28425575
Tabrizi, R, et al. (2019), ‘The effects of curcumin-containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials.’, Phytother Res, 33 (2), 253-62. PubMed: 30402990
Weylandt, KH, et al. (2011), ‘Suppressed liver tumorigenesis in fat-1 mice with elevated omega-3 fatty acids is associated with increased omega-3 derived lipid mediators and reduced TNF-α.’, Carcinogenesis, 32 (6), 897-903. PubMed: 21421544