Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

Interleukin-6 compared to the other Th17/Treg related cytokines in inflammatory bowel disease and colorectal cancer

BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further influence the inflammation and the carcinogenesis process.AIM To compare cytokine patterns of active IBD patients with early and advanced CRC.METHODS Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein levels.RESULTS We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD patients.After stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced CRC.The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.CONCLUSION Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC development.The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.

IL-36 Cytokine Expression and Its Relationship with p38 MAPK and NF-κB Pathways in Psoriasis Vulgaris Skin Lesions

Summary： This study examined the correlation of the expression of interleukin-36 （IL-36）, a novel member of interleukin-1 （IL-1） family, with p38 mitogen-activated protein kinase （p38 MAPK） and nu clear factor-kappa B （NF-kB） pathways in psoriasis vulgaris skin lesions. The expression levels of IL-36a, IL-3613, IL-367, phosphorylated p38 MAPK, and NF-id3p65 were detected in the skin tissues of 38 psoriasis patients and 17 healthy control subjects by real-time quantitative reverse transcription po lymerase chain reaction （qRT-PCR） and Western blotting. The cytokine expression levels were com pared between the psoriasis group and the control group. A correlation analysis between cytokine pro teins was performed in the psoriasis group. Results showed that the expression levels of IL-36a, IL-3613, IL-36y, phosphorylated p38 MAPK and NF-rh3p65 in the psoriasis group were Significantly higher than those in the control group （P〈0.001）. In the psoriasis group, the IL-36 cytokine expression was positively correlated with phosphorylated p38 MAPK and NF-kBp65 expression （P〈0.05）. A significant positive correlation was also found between the phosphorylated p38 MAPK and NF-v,.Bp65 expression （P〈0.01）. It was concluded that the increased IL-36 expression is correlated with p38 MAPK and NF-kB pathways in psoriasis vulgaris skin lesions. All the three factors may be jointly involved in the pathogenesis and local inflammatory response of psoriasis.

Low interleukin-10 level indicates a good prognosis in Salmonella enterica serovar typhimurium-induced pediatric hemophagocytic lymphohistiocytosis:A case report

BACKGROUND Secondary hemophagocytic lymphohistiocytosis(sHLH)triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients.There is no consensus on how to treat S.typhimurium-triggered sHLH.CASE SUMMARY A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S.typhimurium,human rhinovirus,and Mycoplasma pneumoniae infections.At the time of admission to our institution,the patient’s T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6(IL-6),9.1 pg/mL for IL-10,and 246.7 pg/mL for interferon-gamma(IFN-γ),for which the ratio of IL-10 to IFN-γwas 0.04.In this study,the patient received meropenem,linezolid,and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy(10 mg/kg/d for 3 d)and antishock supportive treatment twice.After careful evaluation,this patient did not receive HLH chemotherapy and recovered well.CONCLUSION S.Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ≤1.33,an IL-10 concentration≤10.0 pg/mL,and/or an IFN-γconcentration≤225 pg/mL at admission.Early antimicrobial and supportive treatment was sufficient,and the HLH-94/2004 protocol was not necessary under these conditions.

Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.

Mucosal cytokine network in inflammatory bowel disease

Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are characterized by ongoing mucosal inflammation in which dysfunction of the host immunologic response against dietary factors and commensal bacteria is involved. The chronic in-flammatory process leads to disruption of the epithelial barrier, and the formation of epithelial ulceration. This permits easy access for the luminal microbiota and dietary antigens to cells resident in the lamina pro-pria, and stimulates further pathological immune cell responses. Cytokines are essential mediators of the interactions between activated immune cells and non-immune cells, including epithelial and mesenchymal cells. The clinical efficacy of targeting TNF-α clearly indicates that cytokines are the therapeutic targets in IBD patients. In this manuscript, we focus on the bio-logical activities of recently-reported cytokines [Inter-leukin (IL)-17 cytokine family, IL-31 and IL-32], which might play a role through interaction with TNF-α in the pathophysiology of IBD.

Study of the mechanisms of acupuncture and moxibustion treatmentfor ulcerative colitis ratsinview of the gene expression of cytokines

AIM:To observe the effect of acupuncture and moxibustion on the expression of IL-1beta and IL-6 mRNA in ulcerative colitis rats.METHODS:The SD rat ulcerative colitis model was created by immunological method associated with local stimulation. Colonic mucosa was prepared from human fresh surgical colonic specimens, homogenized by adding appropriate amount of normal saline and centrifuged at 3000r/min. The supernatant was collected for measurement of protein conentration and then mixed with Freund adjuvant. This antigen fluid was first injected into the plantae of the model group rats, and then into their plantae, dorsa, inguina and abdominal cavities (noFreund adjuvant for the last injection) again on the 10th, 17th, 24th and 31st day. When a certain titer of serum anti colonic antibody was reached, 2% formalin and antigen fluid (no Freund adjuvant) were administered separately by enema. The ulcerative colitis rat model was thus set up. The animals were randomly divided into four groups: model control group (MC, n = 8), electro acupuncture group (EA, n = 8), herbs partition moxibustion group (HPM 8), normal control group (NC,n = 8). HPM: Moxa cones made of refined mugwort floss were placed on the medicinal pad (medicinal pad dispensing: Radix Aconiti praeparata, cortex Cinnamomi, etc) for Qihai (RN 6) and Tianshu (ST 25, bilateral) and ignited. Two moxa cones were used for each acupoint once a day and 14 times in all. EA: Tianshu (bilateral) and Qihai were stimulated by the intermittent pulse with 2Hz frequency, 4mA intensity for 20 minutes once a day and 14 times in all. After treatment, rats of all four groups were killed simultaneously. The spleen was separated and the distal colon was dissected. Total tissue RNA was isolated by the guanidinium thiocyanate phenol chloroform extraction method. RT-PCR technique was used to study the expression of IL-1 beta and IL-6 mRNA.RESULTS:IL-1 beta and IL-6 mRNAs were not detected in the spleen and colonic mucosa of the NC rats, whereas they were significantly expressed in that of the MC rats.IL-1 beta and IL-6 mRNAs were markedly lower in the EA and HPM rats than that in MC rats. There was no significant difference between the levels of IL-1 beta and IL-6 mRNAs in the EA and HPM rats. The expressions of IL-1 beta and IL-6 mRNAs were nearly the same in the spleen and colon of all groups.CONCLUSION:Acupuncture and moxibustion greatly inhibited the expression of IL-1 beta and IL-6 mRNA in the experimental ulcerative colitis rats.

Effect of cholecystokinin on cytokines during endotoxic shock in rats

AIM: To study the effect of cholecystokinin-octapeptide (CCK-8) on systemic hypotension and cytokine production in lipopolysaccharide (LPS)-induced endotoxic shock (ES) rats. METHODS: The changes of blood pressure were observed using physiological record instrument in four groups of rats: LPS (8mg.kg(-1),iv) induced ES; CCK-8 (40 microg.kg(-1), iv) pretreatment 10 min before LPS (8mg.kg(-1)); CCK-8 (40 micro.kg(-1), iv) or normal saline (control) groups. Differences in tissue and circulating specificity of the proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6) were assayed with ELISA kits. RESULTS: CCK-8 reversed LPS-induced decrease of mean artery blood pressure (MABP) in rats. Compared with control, LPS elevated the serum level of IL-6 significantly (3567 +/- 687 ng.L(-1) vs 128 +/- 22 ng.L(-1), P【0.01), while contents of TNF-alpha and IL-1beta elevated significantly (277 +/- 86 ng.L(-1) vs not detectable and 43 +/- 9 ng.L(-1) vsnot detectable, P【0.01) but less extent than IL-6. CCK-8 significantly inhibited the LPS-induced increase in serum TNF-alpha IL-1beta and IL-6. LPS elevated spleen and lung content of IL-1beta significantly (5184 +/- 85 ng.L(-1) vs 1047 +/- 21 ng.L(-1) and 4050 +/- 614 ng.L(-1) vs not detectable, P【0.01), while levels of TNF-alpha and IL-6 also rose significantly but in less extent than IL-1beta. CCK-8 inhibited the LPS-induced increase of the cytokines in spleen and lung. In the heart, CCK-8 significantly inhibited LPS-induced increase of TNF-alpha (864 +/- 123 ng.L(-1) in CCK-8+LPS group vs 1599 +/- 227 ng.L(-1) in LPS group, P 【 0.01), and IL-1beta (282 +/- 93 ng.L(-1) in CCK-8+LPS group vs 621 +/- 145ng.L(-1) in LPS group, P 【 0.01). CONCLUSION: CCK-8 reverses ES, which may be related to its inhibitory effect on the overproduction of cytokines.

Alterations of biliary biochemical constituents and cytokines in infantile hepatitis syndrome

AIM: To investigate the biliary biochemical constituents and cytokines in infantile hepatitis syndrome (IHS). METHODS: From 42 IHS subjects and 21 controls, serum and biliary biochemical constituents, including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GT), total bile acid (TBA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) both in bile and serum, were assayed. The subjects with IHS were divided into a cholestasis group (n = 21) and a hepatitis group (n = 21). RESULTS: In the cholestasis group, serum TBIL, DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01); and also the biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control, whereas biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the cholestasis group, serum IL-6 and TNF-α levels were lower than those in bile (P < 0.01). In the hepatitis group, serum DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01 or 140.57 ± 70.32 vs 79.06 ± 35.25, P < 0.05), while biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control (P < 0.01), and biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the hepatitis group, serum IL-6 and TNF-α levels were also lower than those in bile (P < 0.01). Serum TBIL, DBIL, γ-GT, IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitis group, while biliary IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitisgroup. Biliary IL-6 and TNF-α were found to be more significantly increased than serum IL-6 and TNF-α in IHS (P < 0.01). The biliary IL-6 and TNF-α levels were positively correlated with serum DBIL, TBA and γ-GT levels in IHS subjects. CONCLUSION: Biliary biochemical constituents alter in coincidence with pathological changes in hepatocellular injury. Cholestasis is more serious in IHS patients of cholestasis subtype. Assay of biliary IL-6 and TNF-α levels can be specific and sensitive to determine the inflammatory status of impaired liver in IHS.

HCV-specific cytokine induction in monocytes of patients with different outcomes of hepatitis C

AIM:Cytokine release by macrophages critically determines the type of immune response to an antigen.Therefore,we studied hepatitis C virus(HCV)-specific induction of interleukins-1β,-10,-12(IL-1β,IL-10,IL-12),and tumor necrosis factor-α(TNF-α)in monocytes. METHODS:Intracallular cytokine expression was studied by flow cytometry in 23 patients with chronic hepatitis C,14 anti-HCV seropositives without viremia and 11 controls after stimulation of peripheral blood mononuclear calls with recombinant core,NS3,NS4,NSSa and NSSb proteins. RESULTS:Patients with HCV viremia revealed greater spontaneous expression of IL-1β,TNF-α,and IL-10. Furthermore,greater than twofold higher IL-10 expression was induced by the HCV antigens in chronic hepatitis C than in the other two groups(P<0.05).In contrast,neither IL- 12 nor TNF-α was induced preferentially. CONCLUSION:In chronic hepatitis C antigen-specific cytokine induction in monocytes is apparently shifted towards predominant IL-10 induction-not counterbalanced by antiviral type 1 cytokines.This may contribute to persistent viral replication.

Role of relevant immune-modulators and cytokines in hepatocellular carcinoma and premalignant hepatic lesions

AIM To assess the levels of different immune modulators in patients with hepatocellular carcinoma(HCC),in relation to other hepatic diseases.METHODS Eighty-eight patients were included in the current study and represented patients with HCC(20),liver cirrhosis(28) and chronic hepatitis(CH;25),and normal controls(NC;15).Peripheral blood was isolated for immunophenotyping of active myeloid dendritic cells(m DCs;CD1 c and CD40),mature inactive myeloid cells(CD1 c and HLA),active plasmacytoid cells(p DCs;CD303 and CD40),mature inactive p DCs(CD30 and HLA),active natural killer(NK) cells(CD56 and CD161),active NK cells(CD56 and CD314) and inactive NK cells(CD56 and CD158) was done by flow cytometry.Serum levels of interleukin(IL)-2,IL-10,IL-12,IL-1β,interferon(IFN)-α,IFN-γ and tumor necrosis factor(TNF)-αR2 were assessed by ELISA.RESULTS Active m DCs(CD1 C+/CD40+) and inactive m DCs(CD1 c+/HLA+) were significantly decreased in HCC patients in relation to NC(P < 0.001).CD40+ expression on active p DCs was decreased in HCC patients(P < 0.001),and its level was not significantly changed among other groups.Inactive p DCs(CD303+/HLA+),inactive NKs(CD56+/CD158+) and active NKs(CD56+/CD161+) were not statistically changed among the four groups studied;however,the latter was increased in CH(P < 0.05).NKG2 D was statistically decreased in HCC,CH and cirrhosis(P < 0.001),and it was not expressed in 63%(12/20) of HCC patients.There was significant decrease of IL-2,IFN-α and IFN-γ(P < 0.001),and a significant increase in IL-10,IL-1β,and TNF-αR2(P <0.01,P < 0.001 and P < 0.001;respectively) in HCC patients.There was inverted correlation between IL-12 and IL-1β in HCC(r =-0.565,P < 0.01),with a strong correlation between p DCs(CD303+/CD40+) and NKs(CD56+/CD161+;r = 0.512,P < 0.05) as well as inactive m DCs(CD1 c+/HLA+) and inactive NK cells(CD56+/CD158+;r = 0.945,P < 0.001).CONCLUSION NKG2 D,CD40,IL-2 and IL-10 are important modulators in the development and progression of HCC.

Multi-analyte analysis of cytokines that predict outcomes in patients with hepatocellular carcinoma treated with radiotherapy

AIM To analyze cytokine levels and to identify their association with outcome in patients with hepatocellular carcinoma(HCC) treated with radiotherapy(RT). METHODS Patients with HCC who were treated with RT were eligible for this prospective study. Blood samples were collected before and after RT, and serum cytokine levels including interleukin(IL)-1, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α were analyzed. RESULTS Between 2008 and 2009, 51 patients were enrolled in this study. Baseline IL-6 level was high in patients with a history of pre-RT treatment. Median survival was 13.9 mo with alpha-fetoprotein(AFP) as a significant factor(P = 0.020). Median failure-free survival(FFS) for infield, outfield-intrahepatic and extrahepatic failures were 23.3, 11.5 and 12.0 mo, respectively. Sex and baseline IL-6 level were associated with infield FFS, and baseline IL-10 level was correlated with outfield-intrahepatic FFS. For extrahepatic FFS, AFP was significant(P =0.034). Patients with a baseline IL-6 level of ≥ 9.7 pg/m L showed worse infield FFS(P = 0.005), and this significance was observed only in treatment-non-na?ve patients(P = 0.022). CONCLUSION In addition to AFP, cytokines seem useful in predicting infield and outfield-intrahepatic failure. Serum cytokines could be useful biomarkers for predicting RT outcome in HCC.

Adhesion molecule and proinflammatory cytokine gene expression in hepatic sinusoidal endothelial cells following cecal ligation and puncture

INTRODUCTIONMultiple organ dysfunction syndrome (MODS) isthought to be a frequent consequence of sepsis[1-3].Despite substantial advances in our knowledge and understanding of the basic pathophysiologic mechanisms[4-7], in critically ill patients infections and sepsis are still associated with a high mortality[8,9].

Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease

AIM: To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease.METHODS: We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease(MELD) and Pediatric End Stage Liver Disease(PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition(Z-score <-1.00) and malnutrition(Z-score <-2.00). Interleukin-1β(IL-1β), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. RESULTS: The median(25th-75 th centile) age of the study population was 60(17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease(72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values were increased in patients at nutritional risk(34.9%) compared with those who were well-nourished [7.12(0.58-34.23) pg/m L vs 1.63(0.53-3.43) pg/m L; P = 0.02], correlating inversely with triceps skinfold-for-age z-score(rs =-0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child-Pugh score(P = 0.001). This association remained significant after adjusting for nutritional status in a linear regression model. CONCLUSION: High IL-6 levels were found in children with chronic liver disease at nutritional risk. Inflammatory activity may be related to nutritional status deterioration in these patients.

Moderating effect of synthesized docosahexaenoic acid-enriched phosphatidylcholine on production of Th1 and Th2 cytokine in lipopolysaccharide-induced inflammation

Objective: To evaluate effects of docosahexaenoic acid-enriched phosphatidylcholine(DHAPC) on cytokine production induced by lipopolysaccharide(LPS). Methods: The culture supernatants of splenocytes exposed to DHA-PC along with LPS were harvested to determine the production of Th 1(IFN-kines. Cytokines were m毭 and IL-2) and Th2 [IL-4, IL-5, IL-6 and IL-12/IL-23(p40)] cytoeasured using ELISA. Results: Co-administration of DHAPC with LPS resulted in significantly lower IL-2 expression compared to that observed with administration of only LPS(P<0.01). Treatment with DHA-PC and LPS significantly increased IL-5 expression(P<0.01). Moreover, co-administration of DHA-PC with LPS significantly decreased IL-6 and IL-12/IL-23(p40) expressions compared to that observed with administration of only LPS(P<0.01). Conclusions: Our results suggest that DHA-PC inhibits pro-inflammatory cytokines [IL-2, IL-6 and IL-12/IL-23(p40)] expression on induction of inflammation.

Effect of Black Sea bream extracts on cytokine production inlipopolysaccharide-induced inflammation

We investigated the effect of black sea bream extracts on changes in pro-inflammatory and anti-inflammatory cytokines induced by lipopolysaccharide(LPS)in murine splenocytes.The levels of pro-inflammatory cytokines[interleukin(IL)-6,tumor necrosis factor-α(TNF-α),IL-12/IL-23(p40)and IL-17A]and anti-inflammatory cytokines[IL-4,IL-10 and interferon-γ(IFN-γ)]were assessed.Incubation of murine splenocytes with acetone+methylene chloride(A+M)and methanol(MeOH)extracts significantly decreased LPS-induced IL-6,IL-12/IL-23(p40)and IL-17A productions after 6 h incubation(p<0.05).The A+M and MeOH extracts significantly increased LPS-induced IL-4 and IFN-γproductions at 48 and 72 h incubation(p<0.05).Treatment with A+M extract resulted in significantly higher IL-10 production in splenocytes after 72 h(p<0.05).Conclusively,black sea bream extracts were shown to be efficient in falling several pro-inflammatory cytokines while rising anti-inflammatory cytokines.Thus our results suggest that black sea bream extracts selectivity modulate immune events.

Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes

AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.

Tumor-related cytokine release syndrome in a treatment-naïve patient with lung adenocarcinoma:A case report

BACKGROUND Cytokine release syndrome(CRS)is defined as systemic inflammation that usually occurs following chimeric antigen receptor T-cell therapy administration;however,it has not been reported in patients with untreated non-small cell lung cancer to date.CASE SUMMARY A 44-year-old nonsmoking woman presented to the hospital due to fever,palpitation,nausea,and cough for 1 mo and was diagnosed with stage cT3N3M0(IIIc)adenocarcinoma of the lung.Auxiliary examinations revealed elevated cytokine[tumor necrosis factor-α,interleukin(IL)-1β,and IL-6]and inflammatory factor levels,which decreased after treatment with corticosteroids and immunoglobulin and when tumor growth was controlled following chemotherapy,radiotherapy,and antiangiogenesis therapy.However,tumor recurrence was observed.After administration of nivolumab as third-line treatment,the patient’s condition was transiently controlled;however,CRS-like symptoms suddenly emerged,which led to a resurgence of cytokines and inflammatory factors and rapid death.CONCLUSION CRS can develop in treatment-naïve lung cancer patients.Patients with tumorrelated CRS may be at risk of CRS recurrence,aggravation,and onset of immune checkpoint inhibitor-related adverse events.

Psychological distress and SSRI use predict variation in inflammatory cytokines during pregnancy

Evidence supports the premise that maternal psychological distress adversely affects pregnancy outcomes and that inflammatory markers and placentally-produced corticotrophin-releasing hormone (pCRH) are likely mediating factors. The primary aim of the study was to explore the associations between maternal psychological distress, use of selective serotonin re-uptake inhibitors, pCRH, and maternal plasma inflammatory markers during pregnancy. Measures of maternal plasma pCRH, Interleukins-1, 6, & 10, C-Reactive Protein, Macrophage Migration Inhibitory Factor, and Tumor Necrosis Factor-αwere completed in 100 pregnant women. Measures of depression, anxiety, and perceived stress were completed, as well as collection of demographic/behavioral data, e.g. use of selective serotonin re-uptake inhibitors (SSRIs). Significant correlations were found at 14-20 weeks gestation between IL-6 & 10, and depression, anxiety, and perceived stress. Also at 14 - 20 weeks gestation, IL10 levels were significantly lower in women with 4th quartile pCRH levels and IL1β, IL6, and IL10 were significantly lower among women who took an SSRI during pregnancy. After controlling for maternal age, BMI, pCRH level, and SSRI use, psychological distress remained to explain variation in maternal inflammatory markers. These results might suggest that future research should focus on whether depression and anxiety are effectively being treated during pregnancy, and how such a scenario might contribute to an immune system pathway to poor pregnancy outcome.

Liver dysfunction as a cytokine storm manifestation and prognostic factor for severe COVID-19

patients with or without preexisting liver disorders,posing a significant complication and mortality risk.During coronavirus disease 2019(COVID-19),abnormal liver function is typically observed.However,liver injury may occur because of the treatment as well.Ischemia,cytokine storm,and hypoxia were identified as the three major factors contributing to liver damage during COVID-19.Indeed,raised liver enzymes during hospitalizations may be attributed to medications used,as well as sepsis and shock.As a result,the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14%to 53%.Aminotransferases and bilirubin are found most often elevated.Usually,increased gamma-glutamyltransferase,alkaline phosphatase,and decreased serum albumin levels are demonstrated.Additionally,although there is no specific treatment for COVID-19,many of the drugs used to treat the infection are hepatotoxic.In this mini-review,we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm.Furthermore,data show that liver injury can be an independent predictor of severe COVID-19,the need for hospitalization,and death.