Inflammasomes are high-molecular-weight, multiprotein complexes in cells, which are assembled after cytoplasmic nucleotide-binding oligomerization domain like receptors (NLRs) sense pathogens and danger signals. The inflammasome can activate caspase-1, and later makes the pro-IL-1β, proIL-18 precursor mature by cleavaging, thereby mediates the innate immunity. Dysregulation of inflammasomes plays an important role in the development of sepsis and other immune inflammatory diseases, thus inflammasome may be a new target for prevention and treatment of sepsis.
Caspase 1 ; immunology ; metabolism ; Humans ; Inflammasomes ; chemistry ; immunology ; metabolism ; Interleukin-18 ; immunology ; metabolism ; Interleukin-1beta ; immunology ; metabolism ; Sepsis ; immunology ; metabolism ; Signal Transduction

Inflammasomes are large multi-protein complexes that serve as a platform for caspase-1 activation, and this process induces subsequent maturation and secretion of the proinflammatory cytokines IL-1β and IL-18, as well as pyroptosis. As an important component of the innate immune system, early activation of inflammasomes in a variety of immune cell subsets can mediate inflammatory response and immunological conditions after burn injury. Here, we review the current knowledge of inflammasomes and its role in immunological and inflammatory response at the early stage of burn injury.
Apoptosis ; Burns ; immunology ; Caspase 1 ; metabolism ; Cytokines ; Humans ; Inflammasomes ; physiology ; Inflammation Mediators ; immunology ; Interleukin-18 ; immunology ; physiology ; Interleukin-1beta ; immunology ; physiology

OBJECTIVETo study the role of interleukin(IL)18 and interferon gamma (IFN-Gamma) in the pathogenesis of condyloma acuminatum(CA).

METHODSDouble antibody sandwich ELISA was used to measure the levels of IL-18 and IFN-Gamma in serum of 30 cases of CA.

RESULTThe serum levels of IL-18 and IFN-Gamma of the CA patients were significantly higher than those of normal controls IL-18 132.00 +/-52.92 microg/L compared with 50.79 +/- 23.48 microg/L, P<0.01 IFN-Gamma:80.83 +/-20.46 microg/L compared with 20.71 +/-11.18 microg/L P <0.01) and IL-18 levels were positively correlated with IFN-Gamma concentrations (r=0.754, t=6.081, P <0.01).

CONCLUSIONThese data suggest that during infection of human papilloma viruses, anti-infective immune responses are activated.

Adult ; Condylomata Acuminata ; immunology ; Female ; Humans ; Interferon-gamma ; blood ; Interleukin-18 ; blood ; Male ; Middle Aged

OBJECTIVEThis study examined the changes of serum levels of interleukin (IL)-16, IL-18 and immunoglobulins and the correlation of serum IL-16, IL-18 levels and immunoglobulins in children with asthma and aimed to explore the role of IL-16, IL-18 and immunoglobulins in the pathogenesis of asthma.

METHODSThirty-four children with asthma and 21 age and gender-matched healthy children were enrolled in this study. The levels of IL-16, IL-18 and immunoglobulin E (IgE) were determined using ELISA. Immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) were detected by immunoturbidimetry.

RESULTSThe levels of IL-16, IL-18 and IgE in patients with asthma at both acute attack and convalescence stages were significantly higher than those in healthy controls. An increased IgG and a decreased IgA levels were found in asthmatic patients at the acute attack stage. There was a positive correlation between the IL-16 and IL-18 levels at both acute attack and convalescence stages of asthma (r=0.70, P < 0.01; r=0.70, P < 0.05). The IL-16 level correlated positively with the IgE level at acute attack stage of asthma (r=0.624, P < 0.01).

CONCLUSIONSIL-16, IL-18 and IgE may be involved in the pathogenesis of asthma. The immunologic imbalance exists in children with asthma at both acute attack and convalescence stages. Anti-allergic therapy should be administered through the acute attack to the convalescence stages of asthma.

Adolescent ; Asthma ; etiology ; immunology ; Child ; Child, Preschool ; Female ; Humans ; Immunoglobulins ; blood ; Interleukin-16 ; blood ; Interleukin-18 ; blood ; Male

OBJECTIVETo evaluate the role of interleukin (IL)-18 and IL-18 receptor (IL-18R) in the predominant Th1 type cytokine response in patients with immune thrombocytopenia (ITP).

METHODSFifteen patients with active phase ITP, eighteen in remission and thirteen healthy controls were enrolled in this study. T-bet and GATA-3 mRNA levels in peripheral blood mononucleated cells (PBMNC) were measured by reverse transcriptase polymerase chain reaction (RT-PCR); the plasma IL-18 level by enzyme linked immunosorbent assay (ELISA), the expression of IL-18R on CD3(+) lymphocytes and total lymphocytes by flow cytometry(FCM).

RESULTSThe T-bet mRNA levels in patients with active phase ITP was 3.572 fold as much as that in the controls (P < 0.05), while the GATA-3 mRNA levels were 0.378 fold of that in controls (P < 0.05). The levels of plasma IL-18 and IL-18R on CD3(+) lymphocytes were significantly increased in active phase ITP than in remission phase and controls. There was no difference in ratio of T-bet/GATA-3 between remitted ITP and controls and so was for T-bet mRNA, GATA-3 mRNA, plasma IL-18 and IL-18R on CD3(+) lymphocytes.

CONCLUSIONITP as a disease of Th1-dominant response there is an unbalance between T-bet and GATA-3 in its active phase; IL-18 and IL-18R being upregulated.

Adolescent ; Adult ; Aged ; Case-Control Studies ; Female ; GATA3 Transcription Factor ; metabolism ; Humans ; Interleukin-18 ; immunology ; metabolism ; Male ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic ; immunology ; metabolism ; Receptors, Interleukin-18 ; immunology ; metabolism ; T-Box Domain Proteins ; metabolism ; Th1 Cells ; immunology ; metabolism ; Young Adult

The NLRP3 inflammasome, a protein complex belonging to the family of nucleotide-binding and oligomerization domain like receptors (NLRs), plays a vital role in the innate immune system. It promotes pro-caspase 1 cleavage into active caspase-1, which contributes to maturation and releases of IL-1β and IL-18 in response to the harmful signals and participates in the host immune response and sterile inflammation. Recently a large number of studies have shown that NLRP3 inflammasome closely relates to the pathogenesis of the vascular diseases. NLRP3 inflammasome, which involves in the sterile inflammation of the vascular wall, plays an important role in the pathogenesis of main, middle and small arteries.
Caspase 1 ; immunology ; metabolism ; Gene Expression Regulation ; genetics ; immunology ; Humans ; Inflammasomes ; immunology ; Inflammation ; complications ; genetics ; Interleukin-18 ; genetics ; immunology ; Interleukin-1beta ; genetics ; immunology ; NLR Family, Pyrin Domain-Containing 3 Protein ; immunology ; Signal Transduction ; genetics ; immunology ; Vascular Diseases ; etiology ; genetics ; immunology

OBJECTIVETo study the significance of cytokines in patients with HIV and hepatitis viruses co-infection.

METHODSSerum levels of IL-18 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). HIV-RNA levels were measured in EDTA plasma by quantitative reverse polymerase chain reaction (PCR). CD4(+) lymphocyte counts were determined by four-color Flow cytometry (FCM).

RESULTSThe levels of IL-18 were significantly higher in HIV-infected persons compared with those in controls (P<0.05). With HIV disease progression, IL-18 levels increased while Il-10 levels decreased. HCV patients showed lower levels of IL-18 and IL-10 than those of the co-infection group.

CONCLUSIONUnivariate analyses shows significant co-variables IL-10 in co-infection. Up-regulating IL-18 activity and/or down-regulating IL-10 may be a potential therapy to patients with HIV and hepatitis viruses co-infection.

Acquired Immunodeficiency Syndrome ; complications ; immunology ; Adult ; Female ; HIV-1 ; Hepatitis B ; complications ; immunology ; Hepatitis C ; complications ; immunology ; Humans ; Interleukin-10 ; blood ; Interleukin-18 ; blood ; Male ; Middle Aged ; T-Lymphocytes, Cytotoxic ; immunology ; Th1 Cells ; immunology ; Th2 Cells ; immunology

The progression of renal damage in diabetic nephropathy(DN)is closely related to Nod-like receptor protein3(NLRP3)inflammasome activation. The characteristics of NLRP3 inflammasome activation include the changed expression and combination levels of NLRP3, apoptosis-associated speck-like protein(ASC)and pro-caspase-1, the increased expression levels of caspase-1, interleukin(IL)-1β and IL-18 and the excessive release levels of the relative inflammatory mediators. Its molecular regulative mechanisms involve the activation of multiple signaling pathways including reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway, nuclear factor(NF)-κB pathway, nuclear factor erythroid-related factor 2(Nrf2)pathway, long non-coding RNA(lncRNA)pathway and mitogen-activated protein kinases(MAPKs)pathway. In addition, more importantly, never in mitosis aspergillus-related kinase 7(Nek7), as a kinase regulator, could target-combine with NLRP3 at upstream to activate NLRP3 inflammasome. Some extracts of Chinese herbal medicines(CHMs)such as quercetin, curcumin, cepharanthine, piperine and salidroside, as well as Chinese herbal compound prescriptions such as Wumei Pills both could treat NLRP3 inflammasome to ameliorate inflammatory renal damage in DN. Therefore, accurately clarifying the targets of anti-inflammatory CHMs and Chinese herbal compound prescriptions delaying DN progression by targeting the molecular regulative mechanisms of NLRP3 inflammasome activation will be one of the development directions in the future.
Caspase 1/immunology* ; Diabetes Mellitus/drug therapy* ; Diabetic Nephropathies/immunology* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Inflammasomes/immunology* ; Interleukin-18/immunology* ; Interleukin-1beta/immunology* ; NIMA-Related Kinases ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

OBJECTIVETo investigate the preventive effect of interleukin-18 (IL-18) gene modified mature dendritic cells (mDC) vaccine on airway inflammation in mouse asthma model.

METHODSThe asthma model was induced by injection of ovalbumin (OVA) in BALB/c mice. IL-18 gene modified mouse mature dendritic cells (mDC) were detected by flow cytometry and its capacity of inducing allogeneic T cell responses was examined by mixed lymphocyte reaction (MLR). The OVA-induced asthmatic mice were randomly divided into 6 groups: PBS group, DXM group, mDC group, Ad-LacZ-mDC group, Ad-IL-18-mDC group and control group. The pathological changes in lung tissues were assayed by HE and AB-PAS staining. The numbers of inflammatory cells and percentage of eosinophils (EOS) in bronchoalveolar lavage fluid (BALF) were counted. The levels of IFN-γ IL-4 and IL-13 in culture supernatant of splenocytes were measured by ELISA method. The percentage of CD4(+)CD25(+)Foxp3(+) Treg was assessed by flow cytometry analysis.

RESULTThe vaccine was effective in decreasing the infiltration of EOS and accumulation of airway goblet cells in lung tissues, the numbers of inflammatory cells and percentage of EOS in BALF, and the levels of IL-4 and IL-13 in culture supernatant of splenocytes, and in increasing the levels of IFN-γ in culture supernatant of splenocytes and the percentage of CD4(+)CD25(+)foxP3(+) reg.

CONCLUSIONIL-18 gene modified mDC vaccine has a preventive effect on airway inflammation in OVA-induced asthmatic mice.

Animals ; Asthma ; immunology ; pathology ; prevention & control ; Dendritic Cells ; immunology ; Disease Models, Animal ; Genetic Therapy ; Interleukin-18 ; genetics ; Lung ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; immunology

OBJECTIVESTo investigate the internal links between immune responses and Tregs and cytokine by the expression of T regulatory cells (Tregs), Foxp3 mRNA of different response groups and the detection of cytokine secretion after hepatitis B vaccination.

METHODSBlood samples were collected in different response groups. Real-time fluorescence quantitative PCR was used to detect the expression of Foxp3 mRNA of peripheral blood mononuclear cells; The surface markers CD4 and CD25 in peripheral-blood mononuclear cells were determined by flow cytometry; ELISA tests were used to detect the production level of phytohemagglutinin (PHA) in peripheral blood mononuclear cells, IL -4, IL-12, IL-18 stimulated by HBsAg and (IFN) gamma.

RESULTS(1) Foxp3 expressions in response group and non-response group were higher before or after PHA and HBsAg were stimulated. Differences were statistically significant (P value less than 0.05) ; (2) In peripheral blood, the percentage of CD4+CD25+ Treg of CD4+ T cells in response group (0.59%+/-0.46%) was obviously lower than those in control group (1.30%+/-1.44%) ; (3) Peripheral blood mononuclear cells stimulated by PHA and HbsAg in each group, the concentration of IFNgamma in non-response group [(11.00+/-9.03) IU/ml] was markedly lower than those in response group [(38.88+/-28.16) IU/ml],and differences were statistically significant (P value less than 0.01); (4) In PHA- or HBsAg-stimulated peripheral-blood mononuclear cells, the concentrations of IL-18, IL-4 and IL-12 had no significant difference.

CONCLUSIONSTo some extent, CD4+CD25+Foxp3+ Treg cells may be involved in negative regulation of the immune responses to HBV vaccination. Immune non-response to HBV vaccination may be connected to insufficient secretion of IFNgamma; There was no correlation between the titer of anti-HBs and the expressions of IFNgamma and CD4+CD25+ Foxp3.

Adolescent ; Antibody Formation ; CD4 Antigens ; metabolism ; Female ; Forkhead Transcription Factors ; immunology ; Hepatitis B ; immunology ; prevention & control ; Hepatitis B Vaccines ; immunology ; Hepatitis B virus ; immunology ; Humans ; Interferon-gamma ; immunology ; Interleukin-12 ; immunology ; Interleukin-18 ; immunology ; Interleukin-2 Receptor alpha Subunit ; metabolism ; Interleukin-4 ; immunology ; Male ; T-Lymphocytes, Regulatory ; immunology ; Young Adult