Pro-inflammatory cytokines levels in tears and dry eye disease in Parkinson’s disease

Background:Neuroinflammation is an essential event in Parkinson’s disease(PD).Identifying affordable and less invasive biomarkers to make an early diagnosis and monitor therapeutic strategies should be a priority among researchers.The study’s objective was to measure tear levels of cytokines in subjects with PD and their association with motor features and the presence of dry eye symptoms.Methods:A total of 16 subjects with PD and 16 age-and sex-matched controls were included.Movement Disorders Society-Unified Parkinson’s Disease Rating Scale(MDS-UPDRS),Hoehn and Yahr(HY)stage scale,Montreal Cognitive Assessment(MoCA),tear break-up time(TBUT),blink rate(BR),Dry Eye Questionnaire 5(DEQ-5)were examined,and pro-inflammatory cytokines[interleukin(IL)-1β,IL-6,IL-8,IL-10,IL-12p70 and tumor necrosis factor-alpha(TNF-α)]were quantified in tears using the BD Cytometric Bead Array Human Inflammatory Cytokine Kit.Results:Higher tear TNF-αwere quantified in PD compared to controls(2.94±3.95 vs.0.33±0.49 pg/mL,P=0.008).According to DEQ-5,50.0%(n=8)of PD subjects and 12.5%(n=2)controls had dry eye disease(DED).No differences were found in cytokines concentrations between PD patients with DED compared to those without DED.IL-8 was associated with the HY stage,TBUT,DEQ-5,and a better MoCA score.A higher BR correlated moderately with a lower HY stage(r=−0.645,P=0.007),and DED patients have lower BR in PD(12.14±2.54 vs.9.0±2.06 blinks/minute,P=0.031).Conclusions:PD patients have higher levels of TNF-αin tears than age-and sex-matched HC.IL-8 in tears may be both involved in the severity of the disease and in the development of DED in PD.In addition,our findings suggest that as HY stage increases,indicating a more advanced stage,BR decreases,indicating greater motor impairment.Conversely,the presence of DED is associated with higher levels of bradykinesia in PD patients,suggesting a potential relationship between DED and motor impairment severity.

Omentin-1 prevents inflammation-induced osteoporosis by downregulating the pro-inflammatory cytokines

Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout(omentin-1^(-/-)) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α(TNF-α), we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.

Pro-inflammatory cytokines profiles in Nigerian pregnant women infected with Plasmodium falciparum malaria

Objective:To investigate the pro-inflammatory cytokines profiles in in Nigerian pregnant women infected with Plasmodium falciparum(P.falciparum) malaria.Methods:Peripheral, and placental blood samples were collected from 96 consenting volunteers comprising 76 P.falciparium infected pregnant women and 20 healthy uninfected pregnant women in Ekpoma.Nigeria,and subjected to ELISA for cytokines evaluation.Results:Increased serum concentrations of interferon-gamma(IFN-γ) was observed in infected pregnant women than their uninfected counterparts[(31.2±20.9) pg/mL vs(1.8±0.9) pg/mL]and these differences were statistically significant(χ~2= 26.18,P【0.05).The depressed levels of interleukin-12(IL- 12) seen in peripheral blood of the infected pregnant women than the uninfected women[(13.9±3.6) pg/mL vs(28.4±5.28) pg/mL]respectively was not statistically significant(χ~2= 4.96,P】0.05). The interleukin-6(IL-6) was significantly elevated in infected pregnant women(81.0±26.1 pg/mL) than in the uninfected pregnant women[(25.0±5.0) pg/mL](χ~2 = 29.58,P【0.05).In all, mean cytokines concentration of IL-6,IL-12 and IFN-γin the placental blood from infected pregnant women were(53.5±23.4) pg/mL,(8.7±6.9) pg/mL and(16.4±4.0) pg/mL,respectively. The multigravidae had a higher haemoglobin level of 10.2 g/dL and birth weight of 3 000 g than the primigrivadae with lower haemoglobin level of 7.5 g/dL and birth weight of 2 430 g. Conclusions:The elevated IFN-γamong the malarous pregnant women implicates it as the major cytokine mediator in the host responses to systematic P.falciparum malaria in our locality.

Reduction of pro-inflammatory cytokines in rats following 7-day oral supplementation with a proprietary eggshell membrane-derived product

NEM®?brand eggshell membrane is a novel dietary supplement that has been clinically shown to alleviate arthritis joint pain and stiffness;however the mechanism of action is not well understood. Preliminary evidence from an?in vitro?study of?NEM®?indicated that the mechanism of action may be based on the reduction of pro-inflammatory cytokines.?In vivo?studies were therefore initiated to evaluate the effects of?NEM®?on pro-inflammatory and anti-inflammatory cytokines following oral administration in rats.?NEM®?was administered daily at doses of 6.13 mg/kg bw/day (Study 1), 10.0 mg/kg bw/day (Study 2), or at doses of 0 (control), 26.0 or 52.0 mg/kg bw/day (Study 3) by oral gavage for 7 consecutive days. Inflammation was induced in the Study 3 rats by intraperitoneal injection of lipopolysaccharide. Changes in plasma cytokine levels from baseline following 7 days of oral supplementation with?NEM®?at 6.13 mg/kg bw/ day (Study 1) were statistically significant at Day 8 for IL-2, TIMP-1 and VEGF, at Day 21 for IL-10, and at Day 35 for MCP-1, MCP-3 and TIMP-1, and at 10.0 mg/kg bw/day (Study 2) were statistically significant at Day 8 for VEGF, at Day 21 for MIP-1β, MIP-2 and VEGF, and at Day 35 for MCP-3, MIP-1β, MIP-2 and VEGF. Changes in serum cytokine levels versus control at 26.0 mg/kg bw/day (Study 3) were statistically significant at all time-points for IL-1β?and at 1.5 hours for IL-10, and at 52.0 mg/kg bw/day (Study 3) were statistically significant at 1.5 hours for IFN-γ, IL-1β?and IL-10, and at 3 hours for IL-1β, and at 24 hours for IL-10. Taken together, these studies demonstrate that oral supplementation with?NEM®?can influence both early-phase pro-inflammatory cytokines like IL-1β?and TNF-α?(Study 3), as well as later-phase cytokines like MCP-1, MIP-1α?&?β, RANTES and VEGF (Study 1 & 2). These studies provide a possible basis for the mechanism of action of?NEM®?in vivo.

Pharmacological evaluation of a novel enhydrazone ester (CEE-1) as a dual inhibitor of the release of pro-inflammatory cytokines and prostanoids from human monocytes

CEE-1 (ethyl 4-phenylhydrazinocyclohex-3-en-2-oxo-6-phenyl-1-oate)—a novel enhydrazone ester, was tested in vitro for anti-inflammatory activity against the release of pro-inflammatory cytokine and prostanoid from lipopolysaccharide-activated human monocytes or human monocytic cell line (U937). The effects were compared with those of standard anti-inflammatory drugs dexamethasone and indomethacin. CEE-1 potently and strongly inhibited the release of both tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2). The concentrations producing 50% inhibition (IC50 values) were 2.0 μM and 2.4 μM for TNF-α and PGE2, respectively. At 30 μM, the drug achieved almost complete inhibition of both mediators. Dexamethasone had similar effects but indomethacin inhibited only the PGE2 release, and although CEE-1 was less potent than these two drugs, it had comparable efficacy. The compound appeared to act, at least, in part by inhibiting the up-regulation of the mRNA for TNF-α as well as that of the prostanoid-synthetic enzyme, cyclo-oxygenase-2 (COX-2). However, like dexamethasone, but unlike indomethacin, CEE-1 did not affect COX-2 enzyme function. Thus, the profile of activity of CEE-1 is similar to that of steroids rather than the non-steroidal anti-inflammatory drugs. Structure-activity study showed that the presence of a simple aromatic ring attached via an NH-NH group was critical for activity. At the concentrations that completely inhibited mediator release, the compound displayed no significant in vitro toxicity on the cells. These results show that CEE-1 is a dual inhibitor of the release of cytokines and prostanoids, and therefore could be a potential alternative to steroids in the treatment of inflammatory diseases.

Inflammatory status in chronic renal failure: The role of homocysteinemia and pro-inflammatory cytokines

AIM: To evaluate determinants of inflammatory markers in chronic renal failure patients according to the level of glomerular filtration rate. METHODS: One hundred fifty four patients(Age; 44 ± 06 years, male/female; 66/88) with chronic renal failure(CRF) were divided into 6 groups according to the National Kidney Foundation(NKF) classification. They included 28 primary stage renal failure patients(CRF 1), 28 moderate stage renal failure patients(CRF 2),28 severe stage renal failure patients(CRF 3), 18 endstage renal failure patients(CRF 4), 40 hemodialysis(HD) patients, and 12 peritoneal dialysis(PD) patients. Tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) and C-reactive protein(CRP) were analyzed by immunosorbent assay kit(ELISA)(Cayman Chemical's ACETM EIA kit). Immunoassay methods were used for total homocysteine(tH cy)(fluorescence polarization immunoanalysis HPLC, Perkin Emer 200 series), transferrin(MININEPHTM human transferin kit: ZK070.R), ferritin(ADVIA Centaur) and fibrinogen analysis(ACL 200). Differences between groups were performed using SPSS 20.0 and data are expressed as the mean ± SD.RESULTS: Results showed that in comparison with CRF 1 group and other groups, TNF-α and IL-6 levels were respectively more elevated in HD(16.38 ± 5.52 pg/mL vs 0.39 ± 0.03 pg/mL, 11.05 ± 3.59 pg/mL vs 8.20 ± 0.22 pg/mL, P < 0.001) and PD(14.04 ± 3.40 pg/m L vs 0.39 ± 0.03 pg/m L, 10.15 ± 1.66 pg/m L vs 8.20 ± 0.22 pg/m L, P < 0.001). IL-1β levels were increased in HD(9.63 ± 3.50 pg/m L vs 3.24 ± 0.10 pg/mL, P < 0.001) and CRF 4(7.76 ± 0.66 pg/mL vs 3.24 ± 0.10 pg/m L, P < 0.001) patients than in CRF 1 and in the other groups. Plasma t Hcy levels were higher in HD(32.27 ± 12.08 μmol/L) and PD(28.37 ± 4.98 μmol/L) patients compared to the other groups of CRF(P < 0.001). The serum CRP level was significantly increased in HD(18.17 ± 6.38 mg/L) and PD(17.97 ± 4.85 mg/L) patients compared to the other groups of CRF patients(P < 0.001). The plasma fibrinogen level was more elevated in HD(6.86 ± 1.06 g/L) and CRF 4(6.05 ± 0.57 g/L) than in the other groups(P < 0.001). Furthermore; the ferritin level was higher in HD(169.90 ± 62.16 ng/m L) and PD(90.08 ± 22.09 ng/m L) patients compared to the other groups of CRF(P < 0.001). The serum transferrin value was significantly decreased especially in PD(1.78 ± 0.21 g/L) compared to the other groups(P < 0.001). We found a negative correlationbetween glomerular filtration rate(GFR), TNF-α levels(r =-0.75, P < 0.001), and t Hcy levels(r =-0.68, P < 0.001). We observed a positive correlation between GFR and transferrin levels(r = 0.60, P < 0.001). CONCLUSION: CRF was associated with elevated inflammatory markers. The inflammation was observed at the severe stage of CRF and increases with progression of renal failure.

The Effect of Chloroquine on Pro-Inflammatory Cytokines Levels in Graves’ Disease: Historical Cohort from a Pilot Randomized Controlled Trial

Objectives: Analyzing the trend in the serum inflammatory cytokines levels in a historical cohort of patients treated with combination of chloroquine and methimazole. Material and methods: We analyzed the pro-inflammatory serum cytokines level [Interleukin-6(IL-6), Tumor Necrosis Factor alpha (TNF-α), Interleukin 1 alpha (IL-1 α) and Interferon gamma (INF-γ)] in the stored blood samples of 22 patients with Graves’ disease who previously randomized to receive either chloroquine and methimazole combination therapy or methimazole monotherapy. Total T3, T4 and TSH levels were measured by an enzyme linked immunosorbent assay (ELISA) method (DRG, New York, USA) and the result was published previously. In this study we used an ELISA method (Bender Medsystem Vienna Austria) to measure serum pro-inflammatory cytokines in the first 6 months of trial. Results: No significant differences in serum cytokines concentration were observed between the two treatment groups (p > 0.05). Although it was not statistically significant, serum INF-gamma concentration tended to be lower in the chloroquine group after four months of therapy (p = 0.12). Conclusion: In this study we found changes in the serum thyroid hormones level did not accompany concomitant changes in the serum cytokines levels in two treatment groups. Therefore it is possible that chloroquine reduce serum thyroid hormones levels independent of its immunomodulatory effect.

Effect of simvastatin on pro-inflammatory cytokines after myocardial in farction in rats

Objective: To study the effect of simv astatin on mRNA expression of inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-10, after myocardial infarction (MI) in rats. Methods: The experimental rats were di vided into three groups: Sham operation group (Sham), the rats were performed a left thoracotomy with no ligation of left descending coronary artery (LAD); Myoc ardial infarction control group (MI-C), the rats were performed a left thoracot omy with ligation of LAD; Simvastatin group (MI-S), the rats were performed a l eft thoracotomy with ligation of LAD, and given simvastatin 40 mg/kg body weight per day through gavage, while the other two groups were given equal normal sali ne by gavage. All animals were caged to feed four weeks. After finished, the rat s were killed, and the hearts were harvested and cut into two equal parts at the level of the papillary muscle: one was used to determine mRNA expression of myo cardial cytokines by RT-PCR, and the other was used to measure cytokines by Wes tern blotting and immunohistochemical staining. Results: All the pro-inflammatory cytokines mentioned above showed few expression in Sham opera tion group. In the MI groups (including MI-C and MI-S groups), mRNA expression of each of these cytokines markedly increased compared with the Sham operation group (P<0.01). Compared with MI-C group, the mRNA expression of TNF- α, IL-1β and IL-6 in the MI-S group significant ly reduced (P<0.01), and mRNA expression of IL-10 obviously increased ( P<0.01). Cytokines principally located in cardiomyocytes of non-infarcted ar ea and survived cardiomyocytes of infarcted area, simvastatin could decrease TNF -α, IL-1β, and IL-6 and increase IL-10 by confirmation of immunohistochemical staining. Conclusion: Simvas tatin markedly lowers pro-inflammatory cytokines, and increases inflammatory pr otective cytokine. Its mechanism needs to be elucidated.

Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not clear.This study was to find out whether systemic inflammation plays an important role.Methods:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex assay.The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR.Results:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels.Compared to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly lower.Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation.The levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital stay.Importantly,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection.Conclusions:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

Nε-carboxymethyl-lysine and inflammatory cytokines,markers and mediators of coronary artery disease progression in diabetes

This editorial refers to the article“Comparative analysis of Nε-carboxymethyllysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”,published in the recent issue of the World Journal of Diabetes 2023 is based on glucose metabolism,advanced glycation end products(AGEs),inflammation and adiposity on diabetes and coronary artery disease(CAD).This study has included CAD patients who were stratified according to glycosylated hemoglobin higher than 6.5 and sex-matched.A higher prevalence of hypertension,dyslipidemia,and non-vegetarian diet were found in the diabetic group.These risk factors might influence body weight and adiposity and explain the increment of the left atrium.Although this data was not supported by the study.The diet can also explain the non-enzymatic reactions on lipids,proteins,or nucleic acids and consequently an increment of AGEs.These molecules can emit fluorescence.However,one of the non-fluorescent and most abundant AGEs is Nε-carboxymethyl-lysine(CML).Its association with coronary artery stenosis and severity in the diabetic group might suggest its role as a player in CAD progression.Thus,CML,after binding with its receptor(RAGE),can induce calcification cascade through reactive oxygen species and mitogen-activated protein kinase.Moreover,this interaction AGE-RAGE can cause activation of the transcription nuclear factor-kb and induce inflammatory cytokines.It might explain the relationship between CML and pro-inflammatory cytokines in diabetic and CAD patients.Although this is a population from one center,the determination of CML and inflammatory cytokines might improve the diagnosis of severe and progressive CAD.Future and comparative studies among glycosylated hemoglobin,CML,and other AGE levels according to diagnosis and prognosis value might modify the clinical practice.Although these molecules are irreversible,they can act through a specific receptor inducing a signal transduction that might be modulated by inhibitors,antibodies,or siRNA.Further mechanistic studies might improve the development of future preventive therapies for diabetic patients.

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.

Expression and Clinical Significance of Various Cytokines in Otitis Media

The expression and clinical significance of relevant cytokines in otitis media (OM) are discussed, and the alterations to the pathological state of the otitis media mucosa are further understood through the study of cytokine transduction pathways. More and more studies have shown that relevant cell proliferation and inflammation progression pathways play a role in the development of otitis media, such as the Jun amino-terminal protein kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathway, the NF-κB signaling pathway, and the PI3K/AKT/PTEN pathway, which are involved in the proliferation of the middle ear mucosa during otitis media, which affects the mucosal cilia, motor function, Eustachian tube function, and the mucosal ciliary function. These studies provide new ideas for the treatment of otitis media and further explore the feasibility of immunotherapy in the future treatment of otitis media. In this paper, we present a review of the latest research progress on the expression of various cytokines in otitis media.

Neutralization of interleukin-17A alleviates burn-induced intestinal barrier disruption via reducing pro-inflammatory cytokines in a mouse model

Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.

Serum level changes of inflammatory cytokines in patients with moderate to severe acne vulgaris treated with dual-wavelength laser

Background:Acne vulgaris(AV)is a common inflammatory skin disease.Although various mechanisms have been indicated in the etiopathogenesis of AV,the exact pathophysiology remains unknown.Various lasers have been used to treat AV;however,the serum level changes of inflammatory cytokines after laser therapy have not been elucidated.We aimed to investigate the relationship between inflammatory changes and remission on the opposite side in patients with moderate to severe AV after treating half of the face with 595-and 1064-nm dualwavelength laser.Methods:In total,18 patients(9 male and 9 female)between 16 and 35 years of age with moderate to severe AV were evaluated in the study.Disease severity was classified according to the Pillsbury grading system of acne.Patients were randomized to receive a series of two treatment sessions at intervals of 2 weeks and followed up at 2 weeks after the final treatment.A 3 mL blood sample was drawn from every subject each time,and serum levels of inflammatory cytokines such as interleukin(IL)-6,IL-8,and IL-22 were determined using enzyme-linked immunosorbent assay at baseline and 2 weeks after each treatment.Improvement was determined by a blinded assessment of photographs taken before and after the final evaluation.Results:Inflammation was significantly reduced on both the treated and untreated sides,and symptoms of AV lesions were alleviated.All patients showed a significant increase in serum IL-22 levels after the first laser therapy,with no significant difference in serum IL-6 and IL-8 levels.After the second laser therapy,serum IL-6,IL-8,and IL-22 levels were significantly decreased.No significant side effects such as bruising,edema,hyperpigmentation,hypopigmentation,or scarring were reported.Conclusion:Half-face treatment with 595-and 1064-nm dual-wavelength laser for moderate and severe AV showed a significant effect of full-face remission,which was associated with a gradual decrease in IL-6,IL-8,and IL-22 levels after half-face topical treatment.This suggests that reducing inflammatory cytokine levels in the serum can relieve inflammation in non-therapeutic sites.This laser treatment is effective,economical,and painless.

Conbercept combined with laser photocoagulation in the treatment of diabetic macular edema and its influence on intraocular cytokines

BACKGROUND The prevalence of diabetes mellitus(DM)in China is high,and the base is broad.Diabetic retinopathy(DR)is a critical condition affecting the life and health of a nation and its economic development.DR is a common complication of DM.AIM To investigate the efficacy of laser photocoagulation combined with intravitreal injection of conbercept for treating macular edema.METHODS Overall,130 patients with diabetic macular edema(DME)hospitalized in The Third People’s Hospital of Changzhou from January 2019 to June 2022 were retrospectively included.According to the treatment plan,130 patients with DME were categorized into an observation and a control group,with 65 patients in each group.The control group received laser photocoagulation,and the observation group received laser photocoagulation with intravitreal injection of conbercept.Observe changes in vision,cytokines in the eye and so on.RESULTS The total efficacy rate in the observation group(93.85%)was higher than that in the control group(78.46%)(P<0.05).In both groups,the best corrected visual acuity correction effect improved after treatment,and the observation group was superior to the control group(P<0.05).Retinal thickness and central macular thickness improved after treatment,and the observation group was superior to the control group(P<0.05).The levels of vascular endothelial growth factor,interleukin-6,soluble intercellular adhesion molecule-1,and basic fibroblast growth factor in both groups improved after treatment,and the observation group was superior to the control group(P<0.05).CONCLUSION In patients with macular edema,combining laser photocoagulation and intravitreal injections of conbercept for DME is a more effective and safer strategy to improve vision,and lower intraocular cytokine levels.

Isoquercitrin suppresses the expression of histamine and pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-κB in human KU812 cells

Mast cells and basophils are multifunctional effector cells that contain abundant secretory granules in their cytoplasm. Both cell types are involved in a variety of inflammatory and immune events, producing an array of inflammatory mediators, such as cytokines. The aim of the study was to examine whether isoquercitrin modulates allergic and inflammatory reactions in the human basophilic KU812 cells and to elucidate its influence on the phosphorylation of mitogen-activated protein kinase(MAPK) and nuclear factor(NF)-κB activation. The KU812 cells were stimulated with phorbol-12-myristate 13-acetate plus the calcium ionophore A23187(PMACI). The inhibitory effects of isoquercitrin on the productions of histamine and pro-inflammatory cytokines in the stimulated KU812 cells were measured using cytokine-specific enzyme-linked immunosorbent(ELISA) assays. Western blotting analysis was used to assess the effects of isoquercitrin on the MAPKs and NF-κB protein levels. Our results indicated that the isoquercitrin treatment of PMACI-stimulated KU812 cells significantly reduced the production of histamine and the pro-inflammatory cytokines, such as interleukin(IL)-6, IL-8, IL-1β, and tumor necrosis factor(TNF)-α. The treated cells exhibited decreased phosphorylation of extracellular signal-regulated kinase(ERK), revealing the role of ERK MAPK in isoquercitrin-mediated allergy inhibition. Furthermore, isoquercitrin suppressed the PMACI-mediated activation of NF-κB in the human basophil cells. In conclusion, the results from the present study provide insights into the potential therapeutic use of isoquercitrin for the treatment of inflammatory and allergic reactions.

Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophills and regulation by interleukin 10 during intestinal inflammation

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Thymosin Alpha-1 Inhibits Complete Freund’s Adjuvant-Induced Pain and Production of Microglia-Mediated Pro-inflammatory Cytokines in Spinal Cord

Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems.The immunopotentiator thymosin alpha-1(Tal)has recently been reported to have anti-inflammatory and neuroprotective functions in rodents.However,how Tα1 affects inflammatory pain remains unclear.In the present study,intraperitoneal injection of Tal attenuated complete Freund's adjuvant(CFA)-induced pain hypersensitivity,and decreased the up-regulation of pro-inflammatory cytokines(TNF-α,IL-1β,and IL-6)in inflamed skin and the spinal cord.We found that CFA-induced peripheral inflammation evoked strong microglial activation,but the effect was reversed by Tα1.Notably,Tα1 reversed the CFA-induced up-regulation of vesicular glutamate transporter(VGLUT)and down-regulated the vesicular γ-aminobutyric acid transporter(VGAT)in the spinal cord.Taken together,these results suggest that Tα1 plays a therapeutic role in inflammatory pain and in the modulation of microgliainduced pro-inflammatory cytokine production in addition to mediation of VGLUT and VGAT expression in the spinal cord.

Poly-gamma-glutamic acid from Bacillus subtilis upregulates pro-inflammatory cytokines while inhibiting NLRP3, NLRC4 and AIM2 inflammasome activation

Poly-gamma-glutamic acid(γ-PGA)is a natural,edible and non-toxic polymer synthesized by Bacillus subtilis and is suggested as a safe biomaterial for the use in hydrogels and vaccine adjuvants.However,the effect ofγ-PGA on inflammasome activation has not yet been studied in macrophages.Inflammasomes,which are intracellular multi-protein complexes,promote acute and chronic inflammation via interleukin-1βor interleukin-18 maturation,and they are known targets for metabolic syndromes and cancer.In this study,we observed thatγ-PGA attenuated NLRP3,NLRC4 and AIM2 inflammasome activation,whereas it upregulated pro-inflammatory cytokine expression in human and murine macrophages.Althoughγ-PGA had conflicting effects on cytokine production and maturation,it clearly alleviated the severity of lipopolysaccharide-induced endotoxin shock in an animal model.Thus,we suggestγ-PGA as a candidate to control inflammasome-mediated disorders.

Perspective on inflammatory cytokines in open spinal dysraphism

Myelomeningocele(MMC)is a severe form of spinal dysraphism.Due to the failure of neural tube closure during early embryonic development,the affected part of the spinal cord is left open like a book at the back of the affected child.This malformed part of the spinal cord is not covered by its protective mesodermal and ectodermal derived layers.Consequently,the exposed neural tissue(i.e.,the neural placode)is prone to injuryduring further intra-uterine development.