Association of pro-inflammatory cytokines with PTSd severity in patients treated with omega-3 supplementation – a pilot study

IntroductionAssociation of pro-inflammatory cytokines with severity of various psychiatric disorders is shown. Evidence suggests omega-3 fatty acids reduce psychiatric symptoms due to anti-inflammatory properties.ObjectivesTo evaluate if serum levels of pro-inflammatory cytokines correlate with the intensity of PTSD symptoms, and the observed change in symptoms’ severity induced by omega-3 supplementation.MethodsWe included 26 Croatian Homeland war veterans (aged 39–60) with chronic PTSD and no major comorbidity, who were on stable therapeutic sertraline dose at least three months before recruitment. Levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) were determined by the enzyme-linked immunosorbent assay method. Intensity of PTSD symptomatology was assessed by Clinician-Administered PTSD Scale (CAPS), Hamilton Anxiety Scale (HAM-A) and 17-item Hamilton Depression Scale (17-HAM-D). During 12 weeks, participants took omega-3 capsules (600 mg/day) while continuing sertraline therapy.ResultsMost participants presented with moderate PTSD evaluated by CAPS. At baseline, cytokine levels were not associated with the severity of PTSD symptoms, as measured by all three scales (P ≥ 0.209). After 12 weeks of omega-3 supplementation the severity of PTSD symptoms significantly decreased, on average by 8 to 13% on the psychometric scales per person (P < 0.001 for all). However, no association was found between the change in cytokine levels and the change in scores, induced by omega-3, on the assessed scales (P ≥ 0.730).SummaryCytokine levels are not associated with PTSD severity or with improvement in PTSD symptomatology. At the same time, sertraline therapy supplemented with omega-3 seemed to reduce the severity of PTSD symptoms.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Download Full-text

Impact of loganin on pro-inflammatory cytokines and depression- and anxiety-like behaviors in male diabetic rats

Physiology International ◽

10.1556/2060.105.2018.2.8 ◽

2018 ◽

Vol 105 (2) ◽

pp. 116-126 ◽

Cited By ~ 2

Author(s):

M Rajabi ◽

G Mohaddes ◽

F Farajdokht ◽

S Nayebi Rad ◽

M Mesgari ◽

...

Keyword(s):

Body Weight ◽

Blood Glucose ◽

Inflammatory Cytokines ◽

Diabetic Rats ◽

Assay Method ◽

Enzyme Linked Immunosorbent Assay ◽

Depression And Anxiety ◽

Tnf Α ◽

Immobility Time ◽

Pro Inflammatory Cytokines

Behavioral disturbances are observed in most patients suffering from diabetes. According to some evidence, pro-inflammatory cytokines have a key role both in diabetes and behavioral disorders, such as anxiety and depression. In this study, the effect of chronic administration of loganin, as a bioflavonoid, was investigated on pro-inflammatory cytokines and depression- and anxiety-like behaviors in streptozotocin-induced diabetes in male Wistar rats. Blood levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay method. Depression- and anxiety-like behaviors were evaluated by forced swimming test (FST), elevated plus maze (EPM), and open field test (OFT), respectively. Body weight was also measured before the interventions and after the experiments in all groups. Our findings show that loganin-treated animals had significantly lower serum concentrations of IL-6 and TNF-α compared with the diabetic group. In the EPM test, loganin treatment significantly increased the percentage of the open arm time and open arm entries. Moreover, loganin treatment significantly decreased the grooming time and restored distance traveled and center crossing in the OFT. However, it decreased immobility time in the FST. Loganin treatment also significantly restored body weight gain and attenuated blood glucose changes in the diabetic rats. These results indicate that loganin possibly alleviates depression- and anxiety-like behaviors associated with diabetes through lowering the blood glucose and pro-inflammatory cytokine levels. More research is required to show the exact mechanism of antidepressant and anxiolytic effects of loganin in diabetes.

Download Full-text

Impact of loganin on pro-inflammatory cytokines and depression- and anxiety-like behaviors in male diabetic rats

Physiology International ◽

10.1556/2060.105.2018.1.8 ◽

2018 ◽

Vol 105 (3) ◽

pp. 199-209 ◽

Cited By ~ 10

Author(s):

M Rajabi ◽

G Mohaddes ◽

F Farajdokht ◽

S Nayebi Rad ◽

M Mesgari ◽

...

Keyword(s):

Body Weight ◽

Blood Glucose ◽

Inflammatory Cytokines ◽

Diabetic Rats ◽

Assay Method ◽

Enzyme Linked Immunosorbent Assay ◽

Depression And Anxiety ◽

Tnf Α ◽

Immobility Time ◽

Pro Inflammatory Cytokines

Download Full-text

AB0103 THE AMBIGUOUS ROLE OF TISSUE CYTOKINES IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1226 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1350.1-1351

Author(s):

O. Korolik ◽

В. Zavodovsky ◽

E. Papichev ◽

Y. Polyakova ◽

S. L ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

High Activity ◽

Inflammatory Cytokines ◽

Stage Iii ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Individuals ◽

Fetuin A ◽

High Level ◽

Extraarticular Manifestations ◽

Pro Inflammatory Cytokines

Background:Cytokines stimulate the inflammatory response in the synovial membrane with rheumatoid arthritis (RA), initiate apoptosis of chondrocytes, activation of osteoclasts. The progression of comorbid diseases is also associated with the influence of cytokines. At the same time, anti-inflammatory cytokines are produced in various tissues. Their role in the pathogenesis of RA and its complications is ambiguous.Adiponectin (A) and Fetuin A (FA) are classified as negative acute phase proteins. Their concentration decreases with an increase in the level of pro-inflammatory cytokines: TNF-α, IL-1 and IL-6. Molecules A and FA, regardless of various factors and from each other, have similar effects in relation to pro-inflammatory cytokines, lipid and carbohydrate metabolism.Visfatin (V) and Nesfatin-1 (N-1) are pro-inflammatory adipokines. B is produced by cells of the mononuclear phagocytic system and connective tissue. N-1 - is produced by the cells of the intermediate and medulla oblongata and by the cells of the gastric mucosa.Objectives:to study the correlation of B, H-1, A and FA with the severity of inflammation in RAMethods:60 patients with RA and 30 healthy individuals were examined. The level of cytokines was determined by an indirect enzyme-linked immunosorbent assay using commercial test systems (Bio Vendor, cat No. RD195023100, Bio Vendor Human Fetuin-A, RaiBiotech, cat No. EIA-VIS-1, RaiBiotech, cat No. EIA-NESF). All patients underwent a full examination. Diagnosed with 2010 EULAR / ACR recommendations.Results:A decreased level of A (less than 0.8 μg/ml) was detected in 15 patients (25%), F-A (less than 653.55 μg/ml) in 16 (27%), a high level of V (more than 39 ng/ml) - in 55 (91%), N-1 (more than 37.95 ng/ml) - in 36 (60%), which is significantly more often than in healthy individuals. No significant difference in the levels of determined adipokines was found depending on the gender and body weight of patients with RA. The level of cytokines in RA is associated with high activity according to DAS 28, positivity by Anti-CCP, extraarticular manifestations of RA. The greatest correlation with extraarticular manifestations is with cutaneous and cerebral vasculitis. The levels of FA and N-1 also correlated with more pronounced radiological changes (X-ray stage III). FA circulating inhibitor of ectopic calcification. N-1 level is positively correlated with systolic blood pressure.Conclusion:A low level of A and FA, a high level of V and N-1 is characteristic of RA with the presence of high activity and positivity in the RF and Anti-CCP. An increased level of B is determined by more than 90% of patients, which indicates its high pro-inflammatory activity. The level of F and N-1 is also associated with the degree of damage to bone tissue (stage III, a lot of erosion). A positive correlation of level V and N-1, negative A and FA with the severity of inflammation in RA confirms the involvement of these proteins in the pathogenesis. A high level of A and V increases the risk of developing cardiovascular diseases and their complications, the effect of N-1 and FA is being studied. The effect of cytokines on osteoclasts and osteoblasts in RA is ambiguousReferences:[1]Visfatin and Rheumatoid Arthritis: Pathogenetic Implications and Clinical Utility. Polyakova Y. Curr Rheumatol Rev.2019[2]Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Kvlividze T. Klinicheskaya Laboratornaya Diagnostika.2019; 64 (1):53-56 (in Russ)[3]Fetuin-A. Novel hepatokine in rheumatoid arthritis laboratory diagnostics. Papichev E. Klinicheskaya Laboratornaya Diagnostika.2018; 63 (12):756-760 (in Russ)Disclosure of Interests:None declared

Download Full-text

Lack of elevation in plasma levels of pro-inflammatory cytokines in common rodent models of pulmonary arterial hypertension: questions of construct validity for human patients

Pulmonary Circulation ◽

10.1177/2045893217705878 ◽

2017 ◽

Vol 7 (2) ◽

pp. 476-485 ◽

Cited By ~ 6

Author(s):

Kenny Schlosser ◽

Mohamad Taha ◽

Yupu Deng ◽

Baohua Jiang ◽

Lauralyn A McIntyre ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Animal Models ◽

Arterial Hypertension ◽

Inflammatory Cytokines ◽

Plasma Levels ◽

Rodent Models ◽

Plasma Cytokine ◽

Cytokine Levels ◽

Pulmonary Arterial ◽

Pro Inflammatory Cytokines

Translational research depends on the relevance of animal models and how well they replicate human disease. Here, we investigated plasma levels of three important pro-inflammatory cytokines (TNFα, IL-6, and MCP-1), known to be elevated in human pulmonary arterial hypertension (PAH), and systematically assessed their levels in PAH patients compared to five different rodent models of pulmonary hypertension (PH). A consistent immunoassay platform (Luminex xMAP) and source (Millipore) was used to measure all specimens. PAH patients (n = 29) exhibited significant elevations in all three cytokines (median [IQR] pg/mL; TNFα, 7.0 [4.8–11.7]; IL-6, 9.2 [3.8–17.2]; MCP-1, 109 [65–142]) versus healthy participants (n = 20) (median [IQR] pg/mL; TNFα, 3.0 [2.0–3.6]; IL-6, 1.7 [0.5–7.2]; MCP-1, 79 [49–93]. In contrast, mice with PH established after three weeks of hypoxia (n = 18) or SU5416 plus hypoxia (n = 20) showed no significant change in their plasma cytokine levels versus controls (n = 16), based on three to four independent experiments per group. Similarly, plasma cytokine levels were not elevated in rats with PH established three weeks after monocrotaline (n = 23), eight weeks after SU5416 alone (n = 10) or six to eight weeks after SU5416 plus hypoxia (n = 21) versus controls (n = 36 rats), based on three to eight independent experiments per group. Positive biologic control specimens from sepsis patients (n = 9), cecal-ligation and puncture (CLP)-induced septic mice (n = 6), and lipopolysaccharide-induced septic rats (n = 4) showed robust elevations in all three cytokines. This study suggests that animal models commonly used for the development of novel diagnostic and therapeutic approaches for PAH may have limited construct validity with respect to markers of systemic immune activation seen in human patients.

Download Full-text

Cytokine Levels in Critically Ill Children With Severe Sepsis and Their Relation With the Severity of Illness and Mortality

Journal of Intensive Care Medicine ◽

10.1177/0885066620912989 ◽

2020 ◽

pp. 088506662091298

Author(s):

Suresh Kumar Angurana ◽

Arun Bansal ◽

Jayashree Muralidharan ◽

Ritu Aggarwal ◽

Sunit Singhi

Keyword(s):

Severe Sepsis ◽

Critically Ill ◽

Inflammatory Cytokines ◽

Severity Of Illness ◽

Critically Ill Children ◽

Positive Correlation ◽

Tnf Α ◽

Cytokine Levels ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Objective: To study the baseline cytokine levels and their relation with the severity of illness and mortality in critically ill children with severe sepsis. Design: Subgroup analysis of a randomized, double-blind, placebo-controlled trial. Setting: Pediatric intensive care unit of a tertiary level teaching hospital in India. Patients: Fifty children with severe sepsis aged 3 months to 12 years. Material and Methods: Blood was collected at admission for estimation of pro-inflammatory (interleukin 6 [IL-6], IL-12p70, IL-17, and tumor necrotic factor α [TNF-α]) and anti-inflammatory (IL-10 and transforming growth factor β1 [TGF-β1]) cytokines. Primary Outcome: To find out correlation between cytokine levels and severity of illness scores (Pediatric Risk of Mortality [PRISM] III score, Sequential Organ Failure Assessment [SOFA], and Vasoactive-Inotropic Score [VIS]). Secondary Outcomes: To compare cytokine levels among survivors and nonsurvivors. Results: Baseline pro-inflammatory cytokine levels (median [interquartile range]) were IL-6: 189 (35-285) pg/mL, IL-12p: 48 (28-98) pg/mL, IL-17: 240 (133-345) pg/mL, and TNF-α: 296 (198-430) pg/mL; anti-inflammatory cytokine levels were IL-10: 185 (62-395) pg/mL and TGF-β1: 204 (92-290) ng/mL. Pro-inflammatory cytokines showed positive correlation with PRISM III score: IL-6 (Spearman correlation coefficient, ρ = 0.273, P = .06), IL-12 (ρ = 0.367, P = .01), IL-17 (ρ = 0.197, P = .17), and TNF-α (ρ = 0.284, P = .05), and anti-inflammatory cytokines showed negative correlation: IL-10 (ρ = −0.257, P = .09) and TGF-β (ρ = −0.238, P = .11). Both SOFA and VIS also showed weak positive correlation with IL-12 (ρ = 0.32, P = .03 and ρ = 0.31, P = .03, respectively). Among nonsurvivors (n = 5), the levels of all the measured pro-inflammatory cytokines were significantly higher as compared to survivors, IL-6: 359 (251-499) pg/mL versus 157 (97-223) pg/mL, P < .0001, IL-12p70: 167 (133-196) pg/mL versus 66 (30-100) pg/mL, P < .0001, IL-17: 400 (333-563) pg/mL versus 237 (122-318) pg/mL, P = .009, and TNF-α: 409 (355-503) pg/mL versus 330 (198-415) pg/mL, P = .002, respectively. Conclusion: In critically ill children with severe sepsis, pro-inflammatory cytokines (especially IL-12p70) showed a weak positive correlation with severity of illness and were significantly higher among nonsurvivors.

Download Full-text

Effect of Omega-3 Fatty Acid Rich Oils; Fish Oil and Perilla Oil on High-Fat Diet Fed DSS-Induced Colitis Mice

Current Developments in Nutrition ◽

10.1093/cdn/nzaa068_010 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1525-1525

Author(s):

Kyung-Ah Kim ◽

Shalom Sara Thomas ◽

Youn-Soo Cha

Keyword(s):

Fish Oil ◽

Inflammatory Cytokines ◽

High Fat Diet ◽

Experimental Colitis ◽

Normal Diet ◽

Protective Effects ◽

Omega 3 ◽

High Fat ◽

Perilla Oil ◽

Pro Inflammatory Cytokines

Abstract Objectives The incidence of inflammatory bowel disease is increasing in newly developing countries, mainly awing to the westernization of the society. Consumption of high-fat diet has known to aggravate colitis. Omega-3 fatty acids are known to have several health benefits including anti-inflammatory effects and some studies have reported the effect of fish oil in experimental colitis. Perilla oil is obtained from the seeds of Perilla frutescens and is known to exert protective effects against obesity, inflammation and hepatic steatosis. We have previously shown that perilla oil has a similar effect like fish oil in high-fat diet induced colon inflammation. In this study, we wanted to investigate the effect fish oil and perilla oil on high-fat-fed, dextran sodium sulfate (DSS)-induced colitis in mice. Methods Six weeks old mice were divided into 4 groups; normal diet without DSS administration (ND), and three high-fat diet with DSS groups; control (HD + DSS), with fish oil supplementation (HDFO+DSS), with perilla oil supplementation (HDPO+DSS). The mice were fed with high-fat diet for 5 weeks prior to DSS administration by water for one week. The mice were sacrificed on the 7th day of DSS administration. Colon length and macroscopic score were measured. The levels of pro-inflammatory cytokines in serum were measured. The stools of the mice were collected for microbial analysis. Results The levels of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β were significantly reduced in FO and PO supplemented groups compared to HD + DSS. The colon length was reduced due to DSS administration compared to ND, and supplementation with FO and PO improved colon length and macroscopic score. Number of Enterobacteriaceae was higher in all DSS administered groups. However, FO and PO treated groups had significantly reduced Enterobacteriaceae. Conclusions The results of this study showed that fish oil and perilla oil exert protective effect against high-fat diet fed DSS-induced colitis. Both fish oil and perilla oil action on colon protection is similar. The experiments to confirm the mechanism of action which includes mRNA and protein analysis are ongoing. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Education).

Download Full-text

SEX-DIMORPHISM IN THE GENOMIC REGULATION OF AGING

Innovation in Aging ◽

10.1093/geroni/igz038.2825 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S768-S769

Author(s):

Bérénice A Benayoun ◽

Ryan A Lu ◽

Nirmal K Sampathkumar

Keyword(s):

Inflammatory Cytokines ◽

Rna Seq ◽

Male Mice ◽

Sex Dimorphism ◽

Exceptional Longevity ◽

Cytokine Levels ◽

Genomic Regulation ◽

Pro Inflammatory Cytokines

Abstract The current cohort of human supercentenarians reveals a surprising predictor for achieving such an exceptional longevity: being female. Indeed, out of 34 living supercentenarians, 33 are women. We obtained samples from 4 and 20 months old female and male mice. Our data indicates that cytokine levels are differentially regulated with age in males vs. females, with pro-inflammatory cytokines specifically upregulated in the serum of old males, but not females. Because of the central role of macrophages in inflammation and their infiltration in tissues with age, we have generated RNA-seq from purified macrophages of aging animals. Female macrophages displayed ~7-20-fold more transcriptional remodeling with aging than males. Pathways specifically downregulated in females with aging included lysosome, inflammation and phagolysosome. Consistently, our data shows that aged female, but not male macrophages, display decreased phagocytic efficiency. Our results support the notion that there are differences in aging trajectories in female vs. male mice.

Download Full-text

Peripheral interleukin-6 promotes resilience versus susceptibility to inescapable electric stress

Acta Neuropsychiatrica ◽

10.1017/neu.2015.36 ◽

2015 ◽

Vol 27 (5) ◽

pp. 312-316 ◽

Cited By ~ 28

Author(s):

Chun Yang ◽

Yukihiko Shirayama ◽

Ji-Chun Zhang ◽

Qian Ren ◽

Kenji Hashimoto

Keyword(s):

Prefrontal Cortex ◽

Western Blot ◽

Inflammatory Cytokines ◽

Learned Helplessness ◽

Blot Analysis ◽

Interleukin 6 ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Electric Stress ◽

Pro Inflammatory Cytokines

ObjectiveAccumulating evidences suggest that pro-inflammatory cytokines such as interleukin-6 (IL-6) play a role in the pathophysiology of depression. In the learned helplessness (LH) paradigm, ~35% rats are resilient to inescapable stress.MethodsLevels of IL-6 in the serum and medial prefrontal cortex (mPFC) of LH rats (susceptible) and non-LH rats (resilience) were measured using enzyme-linked immunosorbent assay and western blot analysis, respectively.ResultsSerum levels of IL-6 in the LH rats were significantly higher than those of control and non-LH rats. In contrast, tissue levels of IL-6 in the mPFC were not different among three groups.ConclusionThe results suggest that peripheral IL-6 may contribute to resilience versus susceptibility to inescapable stress.

Download Full-text

Cutaneous glucocorticoid receptor sensitivity and pro-inflammatory cytokine levels in antidepressant-resistant depression

Psychological Medicine ◽

10.1017/s003329170500632x ◽

2005 ◽

Vol 36 (1) ◽

pp. 37-43 ◽

Cited By ~ 51

Author(s):

PETER FITZGERALD ◽

SINEAD M. O'BRIEN ◽

PAUL SCULLY ◽

KIM RIJKERS ◽

LUCINDA V. SCOTT ◽

...

Keyword(s):

Glucocorticoid Receptor ◽

Inflammatory Cytokines ◽

Topical Steroid ◽

Depression Scale ◽

Topical Steroids ◽

Hamilton Depression Scale ◽

Tnf Α ◽

Resistant Depression ◽

The Impact ◽

Pro Inflammatory Cytokines

Background. There is evidence to indicate that peripheral glucocorticoid receptor (GR) function is reduced in major depression, and a possible molecular explanation for this is the impact of raised pro-inflammatory cytokines. The topical steroid vasoconstriction assay provides a convenient probe of peripheral GR function. The present study sought to assess the sensitivity of peripheral GRs in antidepressant-resistant major depressives and investigate the association between GR sensitivity and circulating plasma cytokines.Method. Nineteen antidepressant-resistant depressives together with age- and sex-matched healthy controls underwent the steroid vasoconstriction assay using three commercial preparations of corticosteroids containing clobetasol propionate 0·05%, betamethasone valerate 0·1%, and clobetasone butyrate 0·05%, corresponding to very potent, potent, and moderately potent steroid creams respectively. The pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured using enzyme-linked immunosorbent assays. The severity of the depressive episode was assessed using the Hamilton Depression Scale (HAMD).Results. Depressed subjects had a significantly reduced vasoconstriction response across all three strengths of steroid. They also had significantly higher concentrations of TNF-α and IL-6. There was a significant inverse correlation between TNF-α concentration and vasoconstriction response and also between the HAMD score and vasoconstriction response.Conclusions. These findings suggest that cutaneous GR function is abnormal in antidepressant-resistant depression, that circulating TNF-α may play a significant role in this abnormality and that the efficacy of topical steroids in antidepressant-resistant depressives is reduced.

Download Full-text