Interleukin 1βreceptor and synaptic dysfunction in recurrent brain infection with Herpes simplex virus type-1

Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.

Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

脑出血大鼠心肌组织IL-1β蛋白表达的变化及扶正护脑胶囊的干预作用

目的:观察脑出血大鼠心肌组织IL-1β蛋白表达的变化及扶正护脑胶囊的干预作用。方法:大鼠随机分为假手术组、模型组、扶正护脑组和安宫牛黄组,分别于术后6、24、72h 3个时相点取材,采用免疫组织化学法测定心肌组织IL-1β蛋白表达,通过图像分析测定IOD值,并与血清CK-MB、cTnI含量作相关性分析。结果:IL-1β阳性颗粒主要在心内膜下的心肌细胞和血管内皮细胞的胞浆中表达。模型组各时间点心肌组织IL-1β蛋白表达均显著升高,其IOD值亦明显升高,扶正护脑组和安宫牛黄组均能明显降低IL-1β蛋白的表达,降低其IOD值。IOD值与cTnI含量呈显著正相关。结论:炎性因子IL-1β参与了脑出血诱发心肌损伤的机制,扶正护脑胶囊通过抑制IL-1β的蛋白表达减轻脑出血后心肌的损伤。

Interleukin-1 and TNF-α polymorphisms and Helicobacter pylori in a Brazilian Amazon population

AIM： To study the association between Interleukin-1 （IL-1） and tumor necrosis factor （TNF）-α polymorphisms, infection by Helicobacter pylori （H pylori） and the development of gastrointestinal diseases.METHODS： Genomic DNA was extracted from the peripheral blood of 177 patients with various gastrointestinal diseases and from 100 healthy volunteers. The polymorphisms in IL-1β and TNF-α genes were analyzed using the polymerase chain reactionrestriction fragment length polymorphism method （PCRRFLP） and those from IL-1RN with PCR. The presence of infection due to H pylori and the presence of the CagA toxin were detected by serology. The histopathological parameters in the gastric biopsies of the patients were according to the Sydney classification.RESULTS： A comparison of the frequencies of the different polymorphisms studied among the patients and the control group demonstrated that the allele IL- 1RN＊2 was more frequent among patients with gastric ulcers and adenocarcinoma. Carriers of the allele IL- RN＊2 and those with reactive serology for anti-CagA IgG had a greater risk of developing peptic ulcer and gastric adenocarcinoma, as well as a higher degree of inflammation and neutrophilic activity in the gastricCONCLUSION： Our results indicate a positive association between IL-1RN gene polymorphism and infection by positive H pylori CagA strains and the development of gastric ulcers and adenocarcinoma.

Protective effect of recombinant human IL-1Ra on CCl_4-induced acute liver injury in mice

AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl 4 ). METHODS: Acute liver damage was induced by injecting 8-wk-old mice with CCl 4 1 mL/kg (1:3 dilution in corn oil) intraperitoneally (ip). Survival after liver failure was assessed by injecting 8-wk-old mice with a lethal dose of CCl 4 2.6 mL/kg (1:1 dilution in corn oil) ip. Mice were subcutaneously injected with 1 mg/kg recombinant human IL-1Ra twice a day after CCl 4 treatment for 5 d. Serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels were determined with a commercial assay kit. Serum IL-1β, IL-1Ra levels were measured by enzyme-linked immunosorbent assay kit. Quantitative real-time polymerase chain reaction was used to determine liver IL-1β, IL-1Ra and IL-6 expression during CCl 4-induced acute liver injury. Liver sections were stained with hematoxylin-eosin. A histology-injury grading system was used to evaluate the degree of necrosis after acute liver injury. Proliferating cell nuclear antigen (PCNA) staining was used to evaluate the role of rhIL-1Ra in promoting hepatocyte proliferation. RESULTS: Quantitative analysis showed a higher level of IL-6 mRNA expression and reduced serum AST and ALT levels in the livers of the rhIL-1Ra-treated group at the early phase of CCl 4-induced acute liver injury. Histological examination indicated a decrease in centrilobular necrotic areas in mice treated with rhIL-1Ra, and a novel role of rhIL-1Ra in promoting hepatocyte proliferation was also supported by an increase of PCNA staining. All these results, accompanied by a strong survival benefit in rhIL-1Ra-treated vs PBS-treated groups, demonstrated that rhIL-1Ra administration ameliorated the histological damage and accelerated the regeneration and recovery process of the liver. CONCLUSION: rhIL-1Ra could be further developed as a novel therapeutic agent for the treatment of acute liver injury because of its ability to reduce hepatocellular damage and facilitate liver regeneration.

Molecular characterization of an IL-1β gene from the large yellow croaker（Larimichthys crocea） and its effect on fish defense against Vibrio alginolyticus infection

Interleukin 1β（IL-1β）, the first interleukin to be characterized, plays a key role in regulating the immune response. In this study, we determined the c DNA and genomic DNA sequences of the IL-1β gene from the large yellow croaker, Larimichthys crocea. Phylogenetic analysis indicated that the IL-1β（Lc IL-1β） gene was most closely related to that of European seabass（Dicentrarchus labrax）, sharing 67.8% amino acid identity. In healthy large yellow croaker, Lc IL-1β transcription was detected in all tested tissues, with the highest level found in the head kidney. Upon Vibrio alginolyticus infection, Lc IL-1β transcription in all tested tissues was significantly upregulated. Intraperitoneal injection of recombinant Lc IL-1β（r Lc IL-1β） improved the survival rate and reduced the tissue bacterial load after V. alginolyticus infection. In addition, r Lc IL-1β induced monocytes/macrophages（MO/MΦ） chemotaxis and increased phagocytosis and bactericidal activity in vitro. These results suggest that Lc IL-1β plays an important role in the large yellow croaker immune response against V. alginolyticus.

Associations between interleukin-1 polymorphisms and gastric cancers among three ethnicities

AIM:To investigate the associations between interleukin(IL)-1B and IL-1RN polymorphisms and gastric cancers among the Tibet,Hui and Han ethnicities.METHODS:Genomic DNA was extracted from peripheral blood of 210,205,and 202 healthy volunteers and from 155,158,and 197 gastric cancer patients from the Tibet,Hui,and Han populations,respectively.Polymorphisms in IL-1B and IL-1RN were analyzed by denaturing high-performance liquid chromatography.RESULTS:Carriers of the IL-1B-31 CC genotype had an increased risk of intestinal type gastric cancer [odds ratio(OR) = 2.17,P = 0.037] in the Tibet ethnicity.Carriers of the IL-1B 2/L genotype had an increased risk of both intestinal and diffuse types of gastric cancer(OR = 2.08,2.31,P = 0.007,0.016,respectively) in the Hui ethnicity.In the Han population,carriers of the IL-1B-31 CC,IL-1B-511CT,TT genotypes had increased risk of intestinal type gastric cancer(OR = 2.51,2.74,5.66,P = 0.005,0.002,0.000,respectively).CONCLUSION:IL-1B and IL-RN genotypes may differentially contribute to gastric cancer among the Tibet,Hui,and Han ethnicities in the Qinghai area of China.

The Experimental Study on the Effect Calcitonin Gene related Peptide on Bone Resorption Mediated by Interleukin-1

To investigate the effect of calcitonin gene related peptide (CGRP) on bone resorption mediated by interleukin 1β(IL 1β) in vitro , the osteoclasts isolated from the long bones of newborn SD rats were co cultured with osteoblasts on ivory slices placed in 24 well plates . 24 h later, conditioned media containing CGRP and/or IL 1β were added to the wells respectively, and continued culturing for 48 h. After the cells were stripped off by ultrasonication, the ivory slices were stained in toludine blue. The number and the total area of resorption lacunae on each slice were measured by computer imaging analysis system. Our results showed that IL 1β significantly stimulated bone resorption, but CGRP inhibited the effect mediated by IL 1β in a dose dependent manner. It is suggested that CGRP may inhibit osteoclastic bone resorption through two ways: One is that CGRP functions directly on osteoclasts to block their activation; the other is that CGRP regulates the release of cytokines by osteoblasts and indirectly affects the function of osteoclasts.

Vitamin D differentially regulates Salmonella-induced intestine epithelial autophagy and interleukin-1β expression

AIM To investigate the effects of active vitamin D3 on autophagy and interleukin(IL)-1β expression in Salmonella-infected intestinal epithelial cells(IECs).METHODS Caco-2 cells, NOD2 siR NA-, Atg16L1 siR NA- or vitamin D receptor(VDR) siR NA-transfected Caco-2 cells were pretreated with 1,25-dihydroxyvitamin D3(1,25D3), and then infected by wild-type S. typhimurium strain SL1344. The conversion of LC3-I to LC3-II was detected by Western blot analysis and LC3+ autophagosome was analyzed by immunofluorescence. Caco-2 cells or VDR si RNA-transfected cells were pretreated with 1,25D3, and then infected by SL1344. Membrane protein and total RNA were analyzed by Western blot and RT-PCR for VDR and Atg16L1 protein and m RNA expression, respectively. Atg16L1 si RNA-transfected Caco-2 cells were pretreated by 1,25D3 and then infected with SL1344. Total RNA was analyzed by RT-PCR for IL-1β mR NA expression.RESULTS The active form of vitamin D, 1,25D3, showed enhanced VDR-mediated Atg16L1 mR NA expression, membranous Atg16L1 protein expression leading to autophagic LC3 II proteins expression and LC3 punctae in Salmonella-infected Caco-2 cells which was counteracted by Atg16L1 and VDR si RNA, but Atg16L1 mediated suppression of IL-1β expression. Thus, active vitamin D may enhance autophagy but suppress inflammatory IL-1β expression in Salmonella-infected IECs.CONCLUSION Active vitamin D might enhance autophagic clearance of Salmonella infection, while modulation of inflammatory responses prevents the host from detrimental effects of overwhelming inflammation.

白细胞介素1β基因＋3954T/C多态性与乳腺癌易患性相关性研究

目的 探讨白细胞介素1β（IL-1β）基因＋3954T/ C 多态性与乳腺癌易患性之间的关系.方法乳腺癌组为符合纳入标准并病理学确诊的乳腺癌新发病例223例,对照组为体检中心常规体检的健康女性284例,采用静脉采血分析各项指标后进行统计学分析.结果 IL-1β＋3954（rs1143634）和IL-1RN基因及基因型的频率在乳腺癌组与对照组之间差异无统计学意义（P＞0.05）;在肿瘤增殖抗原（ki67）的乳腺癌组中,IL-1β＋3954（rs1143634）位点的C,T转换明显增高[C：96.5%（301/312）比88.8%（119/134）;T：3.5%（11/312）比11.2%（15/134）,P＜0.05];在雌激素受体阴性的乳腺癌患者T等位基因的比例增高,差异有统计学意义[23.0%（32/139）比4.5%（15/332）,P＜0.05].结论 IL-1β基因＋3954T/ C多态性与乳腺癌的易感性无相关性,但在ki67高指数的乳腺癌组中,IL-1β＋3954（rs1143634）位点的C-T转换明显增高,在雌激素受体阴性和人表皮生长因子受体2-的乳腺癌患者中A2的比例增高,SNP可能与乳腺癌的不同分子类型相关.

EFFECTS OF ACUMOXI ON IL2-IFN-NKC IMMUNOREGULATORY NETWORK AND ITS RELATED MACROPHAGE-IL1-Th NETWORK AND ON TUMOR——Observation on the Effect of Acumoxi on the Macrophage-IL1-Th Network and on the Metastasis of Hepatoma

Objective: To observe the effect of acumoxi (acupuncture and moxibustion) on macrophage (Mφ)-lL1-Th net-work and hydroperitoneum hepatoma (H 22) metastasis in mice. Methods: A total of 36 BALB/ c male mice bearing H 22 are randomly divided into control, acupuncture and acumoxi groups with 12 cases in each group. In the later 2 groups, Dazhui (GV 14) and Guanyuan (CV 4) are punctured once daily, continuously for 18 days, and in acumoxi group, the two acupoints were also moxibustioned alternatively with moxa stick once every day. After killing the mice, the tissue samples of the 3 groups are treated routinely step by step and analyzed by means of colorimetric analysis for determining the phagocytic function of the macrophages; and the content of IL1 of the Mφ supernatant is assayed with serum plate agglutination (SPA)-Ig floral hoop method of T helper cell (Th) monoclonal antibody; the weight of the reniportal lymph node, the kidney and the lung, and the number of the cancerous nodes on the pulmonary surface are calculated. Results: After acupuncture and moxibustion treatment, the immunoregulatory network indices of acumoxi group increase obviously compared with those of control group(P<0.01), showing an anti-metastasis effect of acumoxi on H 22. Conclusion: Results of the present study and those of our former research prove that acupuncture and moxibustion can suppress the tumor growth and H 22 metastasis by the enhancement of the immunoregulatory network.

Synergistic effect of interleukin-10-receptor variants in a case of early-onset ulcerative colitis

AIM: To investigated the molecular cause of very early-onset ulcerative colitis (UC) in an 18-mo-old affected child.

Neuronal apoptosis and interleukin 1-beta converting enzyme expression in the frontal cortex and hippocampus of mice with ischemia/reperfusion injury

BACKGROUND： Interleukin 1β-converting enzyme （ICE） gene expression can induce neuronal apoptosis. However, the dynamic changes in ICE gene expression and its effects on neuronal apoptosis under cerebral ischemia/reperfusion conditions remain unclear. OBJECTIVE： To observe neuronal apoptosis and changes in ICE gene expression in the frontal cortex and hippocampus following ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A randomized, controlled animal study was conducted at the Laboratory of Experimental Animal Center, the Second Hospital of Jilin University and Central Laboratory, the Second Hospital of Jilin University, China, from November 2008 to September 2009. MATERIALS： The ICE gene primer sequence （TaKaPa Co., Dalian, China）, FACScan Flow cytometer （Becton Dickinson, Franklin Lakes, N J, USA）, and Perkin Elmer GeneAmp PCR system 2400 （Perkin Elmer, Waltham, MA, USA） were used in this study. METHODS： A total of 45 healthy, adult, male, Kunming mice were randomly assigned to normal control （n = 5）, sham surgery （n = 5）, and model （n = 35） groups. The mice in the model group were equally and randomly subdivided into seven subgroups according to various reperfusion time points （1 hour, 1,3, 7, 14, 28, and 42 days）. Animal models of ischemia/reperfusion injury were established by bilateral carotid artery ligation in the model group. The mice in the sham surgery group only received saline perfusion and surgery for carotid artery exposure. MAIN OUTCOME MEASURES： Neuronal apoptosis in the frontal cortex and hippocampus of mice was measured using flow cytometry. The time course of ICE mRNA levels in the frontal cortex and hippocampus were quantified using reverse transcription-polymerase chain reaction. RESULTS： Neuronal apoptosis in the frontal cortex and hippocampus peaked at 3 days following ischemia/reperfusion injury （P 〈 0.05）. ICE mRNA expression increased in the frontal cortex at 1 day following ischemia/reperfusion injury （P 〈 0.05）, decreased at 3 days, and then peaked at 14 days （P 〈 0.05）. ICE mRNA expression increased in the hippocampus at 3 days following ischemia/reperfusion injury （P 〈 0.05）, peaked at 7 days （P 〈 0.05）, and then decreased gradually to normal levels at 28 days. CONCLUSION： Neuronal apoptosis peaked at 3 days following ischemia/reperfusion injury, and both apoptosis and ICE mRNA levels remained high for 2 weeks after injury. Early apoptosis may result from increased ICE mRNA expression.

Neutralizing peripheral circulating IL1β slows the progression of ALS in a lentivirus-infected OPTN^(E478G)mouse model

Background:Amyotrophic lateral sclerosis(ALS)is irreversible and fatal within 3-5 years,with limited options for treatment.It is imperative to develop a symptom-based treatment that may increase the survival of ALS patients and improve their quality of life.Inflammation status,especially elevated interleukin 1β(IL1β),has been reported to play a critical role in ALS progression.Our study determined that neutralizing circulating IL1βslows down the progression of ALS in an ALS mouse model.Methods:The ALS mouse model was developed by microinjection of lentivirus-carrying OPTN^(E478G)(optineurin,a mutation from ALS patients)into the intra-motor cortex of mice.Peripheral circulating IL1βwas neutralized by injecting anti-IL1βan-tibody into the tail vein.Enzyme-linked immunosorbent assay(ELISA)and real-time polymerase chain reaction(RT-PCR)were carried out to determine the protein and gene expression levels of IL1β.TUNEL assay was used to assess the neural cell death.Immunofluorescent staining of MAP2 and CASP3 was accomplished to evaluate neuronal cell apoptosis.Glial fibrillary acidic protein staining was performed to ana-lyze the number of astrocytes.Rotarod test,grip strength test,balance beam test,and footprint test were conducted to assess the locomotive function after anti-IL1βtreatment.Results:The model revealed that neuroinflammation contributes to ALS progression.ALS mice exhibited elevated neuroinflammation and IL1βsecretion.After anti-IL1βtreatment,ALS mice revealed decreased neural cell death and astrogliosis and gained improved muscle strength and motor ability.Conclusions:Blocking IL1βis a promising strategy to slow down the progression of ALS.

Effect of Interleukin-1β on the Variation of Adenylyl Cyclase Expression in Rats with Seizures Induced by L-Glutamate

Summary: To explore the mechanism of interleukin-1beta ( IL-1β) in the onset of seizure and the effect of IL-1β on the expression of adenylyl cyclase (AC) in rats with seizure induced by L-glutamate. Experimental rats were first injected with IL-1β and then L-glutamate (a dose under the threshold) was injected into the right lateral ventricle. The rats were sacrificed 4 h after the onset of epileptic activity and examined for changes in behavior, immunohistochemistry and compared with those with seizure induced by L-glutamate alone. It was found that the expression of AC in hippocampal and neocortex of rats with seizure induced by IL-1β and L-glutamate were stronger than that of control group (P<0.05), without significant difference found between the L-glutamate group and IL-1β plus L-glutamate group in the expression of AC, the latent period and the severity of seizure. When IL-ra were given (i.c.v.) first, there was no epileptic activity and the expression of AC did not increase. There were no differences in the expression of AC of rats with IL-1ra and that of control rats. But when 2-methyl-2-(carboxycyclopropyl)glycine (MCCG) was given (i.c.v.) first, the strongest expression of AC, the shortest latent period and the the most serious seizure activities were observed. The results indicated that IL-1β could facilitate the onset of epilepsy induced by L-glutamate through IL-1R, metabotropic glutamate receptors might work with IL-1R and the increased expression of AC might be involved in the process.

Effect of Interleukin-1β on the Elevation of Cytoplasmic Free Calcium of the Cultured Hippocampal Neurons Induced by L-Glutamate

To investigate the intracellular mechanism that interleukin 1β (IL 1β) facilitates epileptic seizure and neuronal damage, the effect of IL 1β alone or IL 1β plus glutamate (Glu) on the intracellular free calcium ([Ca 2+ ] i) of single cultured hippocampal neuron was examined by using EPC 9 light electricity measurement system. The results showed that IL 1β of different concentrations (5×10 3 U/L, 10×10 3 U/L, 20×10 3 U/L, 30×10 3 U/L, 50×10 3 U/L, 100×10 3 U/L) failed to affect the neuronal [Ca 2+ ] i, but IL 1β could facilitate the augmentation of neuronal [Ca 2+ ] i induced by Glu in a dose dependent pattern. MK 801 inhibited the effect of Glu on [Ca 2+ ] i, and also inhibited the effect of IL 1β on [Ca 2+ ] i induced by Glu, while verapamil did not influence the effect of Glu or IL 1β. It is concluded that IL 1β, as a neuromodulator, can facilitate the activation of NMDA receptor by Glu, induce the increase of intracellular calcium, which enhances the excitement of neuron.

Protective Effect of Interleukin-1β on Motor Neurons after Sciatic Nerve Injury in Rats

Protective effect of interleukin 1β (IL 1β) on motor neurons was studied after peripheral nerve injury. Twenty Wistar rats were divided into 2 groups randomly. The right sciatic nerve of each rat was resected. After silicon tubulization of sciatic nerve in rat, 15 μl 1 ng/ml IL 1β and PBS solution were injected into the silicon capsule respectively. Enzyme histochemistry was performed to show acetyle cholesterase (AchE) and nitric oxide staining (NOS) activity of spinal α motor neurons in spinal segments 2 weeks later. Neurons were counted and the diameter and cross sectional (c/s) area of neurons were analyzed by using computer image analysis system. The results showed that as compared with the normal side, both enzyme activities significantly changed in motor neurons in PBS group. The diameter and c/s area of both neurons changed significantly too ( P< 0 01). These results suggest that exogenous IL 1β protects α motor neurons from degeneration and necrosis after peripheral nerve injury.

AN EXPERIMENTAL STUDY OF THE INTERLEUKIN 1 LEVELS IN AQUEOUS HUMOR AFTER TRANSSCLERAL FIXATION OF INTRAOCULAR LENSES

Purpose. To study the interleukin 1 (IL-1)levels in aqueous humor after transscleral fixation of in- traocular lenses (IOLs) implantation in rabbits and discuss the effect of IL-1 on postoperative anterior ocular inflammation. Methods. Twenty-seven pigmented rabbits were divided into three groups: GI, transscleral fixation of posterior chamber (PC) IOLs implantation; G2, Lens of rabbits were removed without IOLs implanta- tion; G3, the control group, without surgical intervention. On the 1st, 3rd, 7th and 14th postoperative days, aqueous humor samples were obtained. Methyl thiazolyl tetrazolium (MTT) colormetry was used to detected for the presence of IL-1. The data were analyzed by using analysis of variance of SAS soft ware. Results’ It was found that IL-1 level in aqueous humor was increased after transscleral fixation of I- OLs implantation, IL-1 level reached its maximum on the 14th postoperative days in the IOL implanted group. IL-1 levels on 1st, 3rd, 7th and 14th days postoperatively was significantly higher (P<0. 05) in I- OLs implanted group than that of only extracapsular lenses extraction but no IOLs implantation group and that of the none surgical intervention group. COnclusions.IL-1 levels increased had a close relationship with a specific response to IOL implanta- tion. The increase of IL-1 may be suggested as the principal mediators of immunological and inflammatory responses, so that may play critical role in anterior ocular inflammative response after IOL implantation.

EFFECTS OF PHYTOLACCA ACINOSA POLYSACCHARIDES I ON CYTOTOXICITY OF MACROPHAGES AND ITS PRODUCTION OF TUMOR NECROSIS FACTOR AND INTERLEUKIN 1

The in vivo effects of Phytolacca acinosa poly-saccharides I (PEP-I) on immunologic cytotoxicity of mouse peritoneal macrophages and its production of tumor necrosis factor (TNF) and interleukin 1 (IL-1) were studied. PEP-I 80 or 160 mg kg was given ip twice every 4 day. Both doses were found to have significant enhancing activity on macrophages cytotoxicity against S180 sarcoma cells and malignant transformed fibroblast L929 cells. Peritoneal activated macrophages were incubated with LPS for 2 and 24 hrs to induce TNF and IL-1, respectively. The TNF and IL-1 activities were tested from cytotoxicity against L929 cells in an absorbence assay of enzymatic reaction and proliferation of thymocytes co-stimulated assay separately. The optimal time for TNF production was found on day 8. Significant increases in TNF and IL-1 were observed. In comparison of the effect of PEP-I on TNF with that of known priming agent BCG, there was no difference between them, but PEP-I had a high effect on IL-1. These results suggest that cytotoxicity of macrophages primed by PEP-I is closely related to its TNF and IL-1 production.

Depression following a traumatic brain injury:uncovering cytokine dysregulation as a pathogenic mechanism

A substantial number of individuals have long-lasting adverse effects from a traumatic brain injury（TBI）. Depression is one of these long-term complications that influences many aspects of life. Depression can limit the ability to return to work, and even worsen cognitive function and contribute to dementia. The mechanistic cause for the increased depression risk associated with a TBI remains to be defined. As TBI results in chronic neuroinflammation, and priming of glia to a secondary challenge, the inflammatory theory of depression provides a promising framework for investigating the cause of depression following a TBI. Increases in cytokines similar to those seen in depression in the general population are also increased following a TBI. Biomarker levels of cytokines peak within hours-to-days after the injury, yet pro-inflammatory cytokines may still be elevated above physiological levels months-to-years following TBI, which is the time frame in which post-TBI depression can persist. As tumor necrosis factor α and interleukin 1 can signal directly at the neuronal synapse, pathophysiological levels of these cytokines can detrimentally alter neuronal synaptic physiology. The purpose of this review is to outline the current evidence for the inflammatory hypothesis of depression specifically as it relates to depression following a TBI. Moreover, we will illustrate the potential synaptic mechanisms by which tumor necrosis factor α and interleukin 1 could contribute to depression. The association of inflammation with the development of depression is compelling; however, in the context of post-TBI depression, the role of inflammation is understudied. This review attempts to highlight the need to understand and treat the psychological complications of a TBI, potentially by neuroimmune modulation, as the neuropsychiatric disabilities can have a great impact on the rehabilitation from the injury, and overall quality of life.