No Abstract Available.
Humans ; Interleukin-12* ; Interleukin-18* ; Tuberculosis, Pleural*

In this study, we investigated interleukin (IL)-18 and IL-12 following in vitro stimulation with either the 30-kDa or purified protein derivative (PPD) antigens (Ag) of pleural mononuclear cells from 12 cases of tubercular pleurisy (TB-PMC) and 8 cases of malignant pleurisy (MG-PMC). Ag-stimulated TB-PMC produced significantly more IL-12 than did MG-PMC and the levels correlated with those of IFN - gamma. Although elevated IL-18 levels were found in freshly isolated pleural fluids, in vitro IL-18 production in response to either Ag was dramatically decreased in TB-PMC. Pro-IL-18 mRNA was detected before and after Ag stimulation in TB patients. Supernatants from the Ag-stimulated TB-PMC significantly suppressed IL-18 production in normal peripheral blood mononuclear cells (PBMC) and primary malignant cells over an 18 h incubation period. In addition, this suppressive activity was not inactivated by either heat or trypsin. Our findings imply that modulation of IL-12 and IL-18 levels may contribute to the Th1 elevation induced in human TB-P VIC by the 30-kDa and PPD antigens.
Hot Temperature ; Humans ; Interleukin-12* ; Interleukin-18* ; Interleukins ; Mycobacterium tuberculosis ; Pleurisy ; RNA, Messenger ; Trypsin ; Tuberculosis, Pleural

OBJECTIVES: Inflammation especially the overexpression of inflammasome and inflammatory cytokines, is one of the important reasons that affect the occurrence and development of acute cerebral infarction, including the initiation of cerebral infarction, the progress and recovery of post-infarction injury. This study aims to explore expressions of absent in melanoma 2 (AIM2), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in plasma of patients with acute cerebral infarction and its significance. METHODS: A total of 85 patients with acute cerebral infarction were enrolled in the cerebral infarction group. They were assigned into mild, moderate, and severe groups according to the severity of neurological deficits. They were assigned into small, middle, and large cerebral infarction groups according to the area of cerebral infarction. They were assigned into a good prognosis group and a poor prognosis group according to the Modified Rankin Scale (mRS) score on the 90th day after the onset. A total of 85 healthy controls were selected as a control group. The levels of AIM2, IL-1β, and IL-18 in plasma of the cerebral group and the control group were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The levels of plasma AIM2, IL-1β, and IL-18 in the cerebral infarction group were significantly higher than those in the control group (all CONCLUSIONS Expressions of AIM2, IL-1β, and IL-18 are up-regulated in the plasma of patients with acute cerebral infarction, and they are closely related to the severity of neurological deficit, cerebral infarction area, and prognosis in patients with acute cerebral infarction, suggesting that AIM2, IL-1β, and IL-18 may play an important role in the occurrence and development of acute cerebral infarction.
Cerebral Infarction ; DNA-Binding Proteins ; Humans ; Interleukin-18 ; Interleukin-1beta ; Melanoma ; Plasma ; Stroke

BACKGROUND: IL-18 was originally cloned as a IFN-gamma inducing factor in primed T cells. In synergy with IL-12, IL-18 has been shown to induce strikingly high levels of IFN-gamma production by T cells and to enhance Th1 development. Also this cytokine exerts induction of Th2 development through IL-4 induction. METHODS: Resting CD4+ T cells were sorted by negative selection and activated by anti-CD3 plus anti-CD28 Ab. Expression of IL-12 binding sites, IL-18 binding sites, IL-18Ralpha, and GATA-3 mRNA were analysed by FACS and RT-PCR, respectively. RESULTS: Resting CD4+ T cells expressed IL-18Ralpha chain but not IL-18 binding sites, suggesting a lack of IL-18Rbeta expression. IL-18Ralpha was maintained on the Th1 and Th2 committed cells. IL-18 binding sites were induced on the Th1 but not Th2 cells. Exposure of these cells to IL-18 led to up-regulation of GATA-3 mRNA expression only in Th2 committed cells. To elucidate the relationship between IL-18Ralpha expression and GATA-3 induction by IL-18, Th1 and Th2 committed cells were further cultured in medium with or without IL-12 for 2 days. IL-12 binding sites were maintained on the Th1 and Th2 cells regardless of IL-12 treatment, but IL-18Ralpha expression was rapidly down-regulated on the IL- 12-untreated Th2 cells which did not induce GATA-3 mRNA expression followed by IL-18 stimulation. CONCLUSION: IL-12 supports expression of IL-18Ralpha and GATA-3 mRNA expression was induced by IL-18 through IL-18Ralpha without expression of IL-18 binding site in Th2 cells.
Binding Sites ; Clone Cells ; Interleukin-12* ; Interleukin-18 ; Interleukin-4 ; RNA, Messenger ; T-Lymphocytes ; Th2 Cells* ; Up-Regulation

Detection of pathogen by pattern recognition receptors leads to activation of inflammasome which plays a crucial role in immune system. The inflammasome regulates the release of cytokines, such as interleukin (IL)-1beta, IL-18 and high-mobility group box 1 (HMGB1). Double-stranded RNA-dependent protein kinase (PKR) is a critical component of an inflammatory complex. Recently, the critical role of PKR was reported in regulation of multiple inflammasomes.
Cytokines ; eIF-2 Kinase ; Immune System ; Inflammasomes ; Interleukin-18 ; Interleukins ; Receptors, Pattern Recognition

Chronic inflammation is a critical modulator of carcinogenesis through secretion of inflammatory cytokines, which leads to the formation of an inflammatory microenvironment. In this process, the inflammasome plays an important role in the expression and activation of interleukin (IL)-1β and IL-18 to promote cancer development. The inflammasome is a multiprotein complex consisting of several nucleotide-binding domain and leucine-rich repeat containing receptor, adaptor proteins, and caspase 1 (CASP1). It senses the various intracellular (damage-associated molecular patterns) and extracellular (pathogen-associated molecular patterns) stimuli. A primed inflammasome recruits adaptor proteins, activates CASP1 to enhance the proteolytic cleavage of pro-IL-1β and IL-18, and sends the signal to respond to each insult. Depending on stimuli and cell contexts, several inflammasomes are closely associated with the initiation and promotion of carcinogenesis. In contrast, inflammasomes also show an ambivalent effect on carcinogenesis by enhancing inflammatory cell death (pyroptosis) and repairing damaged tissues. Although the inflammasome plays a controversial role in carcinogenesis, it may be a promising target for human cancer prevention and treatment. A more in-depth study on the role of the inflammasome in carcinogenesis, based on stimuli, cell contexts, and cancer stages, can lead to the development of novel therapeutic strategies against malignant human cancers.
Carcinogenesis ; Caspase 1 ; Cell Death ; Cytokines ; Humans ; Inflammasomes* ; Inflammation ; Interleukin-18 ; Interleukins

Among a number of innate receptors, the nucleotide-binding domain leucine-rich repeat containing (NLR) nucleotide oligomerization domain (NOD)-like receptor families are involved in the recognition of cytosolic pathogen- or danger-associated molecules. Activation of these specific sets of receptors leads to the assembly of a multiprotein complex, the inflammasome, leading to the activation of caspase-1 and maturation of the cytokines interleukin (IL)-1beta, IL-18, and IL-33. Among NLRs, NLR-related protein 3 (NLRP3) is one of the best-characterized receptors that activates the inflammasome. There is no doubt that NLRP3 inflammasome activation is important for host defense and effective pathogen clearance against fungal, bacterial, and viral infection. In addition, mounting evidence indicates that the NLRP3 inflammasome plays a role in a variety of inflammatory diseases, including gout, atherosclerosis, and type II diabetes, as well as under conditions of cellular stress or injury. Here, we review recent advances in our understanding of the role of the NLRP3 inflammasome in host defense and various inflammatory diseases.
Atherosclerosis ; Cytokines ; Cytosol ; Defense Mechanisms ; Gout ; Humans ; Inflammasomes ; Inflammation ; Interleukin-18 ; Interleukins

Based on reporting in the last several years, an impressive but dismal list of cytotoxic chemotherapies that fail to prolong the median overall survival of patients with glioblastoma has prompted the development of treatment protocols designed to interfere with growth-facilitating signaling systems by using non-cytotoxic, non-oncology drugs. Recent recognition of the pro-mobility stimulus, interleukin-18, as a driver of centrifugal glioblastoma cell migration allows potential treatment adjuncts with disulfiram and ritonavir. Disulfiram and ritonavir are well-tolerated, non-cytotoxic, non-oncology chemotherapeutic drugs that are marketed for the treatment of alcoholism and human immunodeficiency virus (HIV) infection, respectively. Both drugs exhibit an interleukin-18-inhibiting function. Given the favorable tolerability profile of disulfiram and ritonavir, the unlikely drug-drug interaction with temozolomide, and the poor prognosis of glioblastoma, trials of addition of disulfiram and ritonavir to current standard initial treatment of glioblastoma would be warranted.
Antineoplastic Agents ; Dacarbazine ; analogs & derivatives ; Disulfiram ; Glioblastoma ; Humans ; Interleukin-18 ; Ritonavir

Humans ; Interleukin-18 ; chemistry ; metabolism ; Pulmonary Fibrosis ; etiology ; pathology ; Silicosis ; complications ; pathology ; physiopathology

BACKGROUNDNumerous studies have evaluated the association between interleukin-18 (IL-18) promoter gene -607C/ A (rs1946518) polymorphism and tuberculosis (TB) risk. However, the results remain apparently conflicting. The aim of this study was to investigate whether IL-18-607C/A polymorphism is associated with susceptibility to TB.

METHODSPublications addressing the association between the IL-18-607C/A polymorphism and TB risk were selected from the Pubmed, Cochrane Library, Embase, CNKI and Wanfang databases. Data were extracted from the studies by two independent reviewers. Statistical analysis was performed using RevMan 5.0.25 and STATA 11.0 software.

RESULTSEight case-control studies with a total of 1166 TB patients and 1734 controls were retrieved. Meta-analysis results showed significant association between IL-18-607C/A polymorphism and TB risk in all comparisons of the A allele versus C allele (OR=1.17, 95% CI 1.05-1.30, P=0.004), AA versus CC (OR=1.43, 95% CI 1.14-1.81, P=0.002), CA+AA versus CC (OR=1.20, 95% CI 1.01-1.42, P=0.04) and AA versus CA+CC (OR=1.30, 95% CI 1.07-1.58, P=0.007). In subgroup analysis by nationality, a significant association between IL-18-607C/A polymorphism and TB risk in the comparisons of A versus C, CA+AA versus CC and AA versus CA+CC (OR=1.22, 95% CI 1.07-1.38, P=0.002; OR=1.31, 95% CI 1.06-1.61, P=0.01; OR=1.32, 95% CI 1.07-1.63, P=0.01, respectively) were found in Chinese population but not in Indian and Iranian populations.

CONCLUSIONThis study suggests that the -607C/A polymorphism of IL-18 gene would be a risk factor for TB, especially in Chinese population. To further evaluate gene-to-gene and gene-to-environment interactions on -607C/A polymorphism and tuberculosis risk, more studies with thousands of patients are required.

Genetic Predisposition to Disease ; genetics ; Humans ; Interleukin-18 ; genetics ; Promoter Regions, Genetic ; genetics ; Tuberculosis ; epidemiology ; genetics