Considering that both innate and adaptive immune responses are involved in the pathogenesis of Crohn's disease(CD), novel therapeutic options have significantly been developed. Biological agents represent an impor...Considering that both innate and adaptive immune responses are involved in the pathogenesis of Crohn's disease(CD), novel therapeutic options have significantly been developed. Biological agents represent an important addition to the conventional treatments for immuno-inflammatory conditions, acting as antagonists of adhesion molecules or various inflammatory cytokines. The interleukin 12(IL-12)/IL-23 common pathway has been found to play a determinant role in the induction of inflammation in adaptive immune responses. In particular, IL-23 promotes the differentiation of na?ve T helper cells into Th17 phenotype with the concomitant secretion of several inflammatory cytokines such as IL-17 and IL-22, whereas IL-12 induces the Th1 polarization and production of critical cytokines such as interferon-γ and tumor necrosis factor. Nowadays, there is increased interest regarding the role of IL-23 as a therapeutic target of CD through the blockage of IL-23 mediated pathways. In this editorial, we focus on the role of IL-12/IL-23 pathway in the regulation of mucosal immunity and in the induction and maintenance of chronic inflammation. In parallel, we critically discuss the available data regarding the therapeutic effect of the IL-12/IL-23 inhibitors and especially of ustekinumab, a human monoclonal antibody which has been recently approved by the United States Food and Drug Administration for the management of moderateto-severe CD and its potential to be used as first-line therapy in everyday clinical practice.展开更多
AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METH...AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.展开更多
Objective： To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma. Methods： Peripheral blood samples were obtained from 20 healthy volunte...Objective： To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma. Methods： Peripheral blood samples were obtained from 20 healthy volunteers and 60 patients with renal cell carcinoma before curative surgery. IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay. Results： Mean serum IL-12 and IL-18 levels were significantly higher in patients with renal cell carcinoma compared with healthy volunteers （P〈0.05） and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed. A positive correlation was observed between serum IL-12 and IL-18 levels （P〈0.05）. In patients with renal cell carcinoma, increasing serum IL-12 and IL-18 levels correlated with pathological stage and Fuhrman grade. Conclusion： Serum IL-12 and IL-18 might be useful tumor markers in patients with renal cell carcinoma.展开更多
The killing effects of lymphocytes on Hela cells expressing interleukin-12 （IL-12） in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression...The killing effects of lymphocytes on Hela cells expressing interleukin-12 （IL-12） in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression of IL-12 in Hela cells was detected quantitatively by ELISA; Changes in killing effects of lymphocytes on Hela cells expressing IL-12 were observed by MTT. It was found that Hela cells could express IL- 12 between 24 h and 72 h after transfection. Killing activity of lymphocytes on Hela cells expressing IL-12 was significantly enhanced. It was concluded by cell transfection technique, Hela cells could express 1L-12 and were more easily killed by lymphocytes.展开更多
To investigate the antitumor activity of IL 12, the induction of differentiation of IL 12 was observed using erythroleukemia cells (FBL 3) as model. After incubation with 200 U/mL IL 12 for 48 h, DNA synthesis of FBL ...To investigate the antitumor activity of IL 12, the induction of differentiation of IL 12 was observed using erythroleukemia cells (FBL 3) as model. After incubation with 200 U/mL IL 12 for 48 h, DNA synthesis of FBL 3 cells in S phase decreased significantly; the expression of CD14 which is the specific marker of monocyte increased, the rate of NBT + cells was apparently higher than that of the untreated FBL 3 cells. After treating FBL 3 cells with IL 12 for 72 h, the expression of 33D1 and NLDC145 which are the specific markers of dendritic cells increased markedly, the surface molecules such as MHC II,B7 1, B7 2, and VCAM 1 were up regulated; morphological observation showed two kinds of cells: some cells had a ruffled surface and plentiful lysosome; the others had many dendritic projections on the surface, and contained numerous mitochondria. Functionally, the IL 12 treated FBL 3 cells could apparently stimulate the proliferation of allogeneic and autologous T lymphocytes, and improve the specific cytotoxic activity of CTL on FBL 3 cells. These results indicated that erythroleukemia cells were induced by IL 12 to differentiate into the monocytes and dendritic cells, then exhibited the antigen presenting function. The data outline a new mechanism for IL 12 to treat leukemia.展开更多
The full-length cDNA encoding the subunits p40 and p35 of human interleukin12(hIL12) were cloned separately by RTPCR, linked together by internal ribosomal entry site (IRES) of encephalomyocarditis virus which initiat...The full-length cDNA encoding the subunits p40 and p35 of human interleukin12(hIL12) were cloned separately by RTPCR, linked together by internal ribosomal entry site (IRES) of encephalomyocarditis virus which initiates capindependent translation to form a dicistronic gene fragment. The dicistronic fragment was placed between the cytomegalovirus (CMV) promoter and SV40 polyA signal to form a dicistronic expression cassette. Subsequently, the dicistronic expression cassette was inserted into E1 region of Ad5 genome in cosmid vector pAx1cw of E1substitution type. By homologous recombination with EcoT22Idigested Ad5 DNATPC in 293 cells, the replicationdeficient recombinant adenoviruses of hIL12 were generated efficiently. After infected with hIL12 recombinant adenoviruses in vitro, 293 cells, human hepatocellular carcinoma cells HepG2, and primary human skin fibroblasts expressed and secreted hIL12 at comparable levels (30～60ng/ 106cells/24hr), which could stimulate the proliferation and IFNγ production of human lymphoblasts. These suggest that the dicistronic adenovirus vector of hIL12 could effectively mediate the expression of bioactive hIL12 and might be used in cancer gene therapy.展开更多
文摘Considering that both innate and adaptive immune responses are involved in the pathogenesis of Crohn's disease(CD), novel therapeutic options have significantly been developed. Biological agents represent an important addition to the conventional treatments for immuno-inflammatory conditions, acting as antagonists of adhesion molecules or various inflammatory cytokines. The interleukin 12(IL-12)/IL-23 common pathway has been found to play a determinant role in the induction of inflammation in adaptive immune responses. In particular, IL-23 promotes the differentiation of na?ve T helper cells into Th17 phenotype with the concomitant secretion of several inflammatory cytokines such as IL-17 and IL-22, whereas IL-12 induces the Th1 polarization and production of critical cytokines such as interferon-γ and tumor necrosis factor. Nowadays, there is increased interest regarding the role of IL-23 as a therapeutic target of CD through the blockage of IL-23 mediated pathways. In this editorial, we focus on the role of IL-12/IL-23 pathway in the regulation of mucosal immunity and in the induction and maintenance of chronic inflammation. In parallel, we critically discuss the available data regarding the therapeutic effect of the IL-12/IL-23 inhibitors and especially of ustekinumab, a human monoclonal antibody which has been recently approved by the United States Food and Drug Administration for the management of moderateto-severe CD and its potential to be used as first-line therapy in everyday clinical practice.
文摘AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.
文摘Objective： To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma. Methods： Peripheral blood samples were obtained from 20 healthy volunteers and 60 patients with renal cell carcinoma before curative surgery. IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay. Results： Mean serum IL-12 and IL-18 levels were significantly higher in patients with renal cell carcinoma compared with healthy volunteers （P〈0.05） and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed. A positive correlation was observed between serum IL-12 and IL-18 levels （P〈0.05）. In patients with renal cell carcinoma, increasing serum IL-12 and IL-18 levels correlated with pathological stage and Fuhrman grade. Conclusion： Serum IL-12 and IL-18 might be useful tumor markers in patients with renal cell carcinoma.
文摘The killing effects of lymphocytes on Hela cells expressing interleukin-12 （IL-12） in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression of IL-12 in Hela cells was detected quantitatively by ELISA; Changes in killing effects of lymphocytes on Hela cells expressing IL-12 were observed by MTT. It was found that Hela cells could express IL- 12 between 24 h and 72 h after transfection. Killing activity of lymphocytes on Hela cells expressing IL-12 was significantly enhanced. It was concluded by cell transfection technique, Hela cells could express 1L-12 and were more easily killed by lymphocytes.
文摘To investigate the antitumor activity of IL 12, the induction of differentiation of IL 12 was observed using erythroleukemia cells (FBL 3) as model. After incubation with 200 U/mL IL 12 for 48 h, DNA synthesis of FBL 3 cells in S phase decreased significantly; the expression of CD14 which is the specific marker of monocyte increased, the rate of NBT + cells was apparently higher than that of the untreated FBL 3 cells. After treating FBL 3 cells with IL 12 for 72 h, the expression of 33D1 and NLDC145 which are the specific markers of dendritic cells increased markedly, the surface molecules such as MHC II,B7 1, B7 2, and VCAM 1 were up regulated; morphological observation showed two kinds of cells: some cells had a ruffled surface and plentiful lysosome; the others had many dendritic projections on the surface, and contained numerous mitochondria. Functionally, the IL 12 treated FBL 3 cells could apparently stimulate the proliferation of allogeneic and autologous T lymphocytes, and improve the specific cytotoxic activity of CTL on FBL 3 cells. These results indicated that erythroleukemia cells were induced by IL 12 to differentiate into the monocytes and dendritic cells, then exhibited the antigen presenting function. The data outline a new mechanism for IL 12 to treat leukemia.
文摘The full-length cDNA encoding the subunits p40 and p35 of human interleukin12(hIL12) were cloned separately by RTPCR, linked together by internal ribosomal entry site (IRES) of encephalomyocarditis virus which initiates capindependent translation to form a dicistronic gene fragment. The dicistronic fragment was placed between the cytomegalovirus (CMV) promoter and SV40 polyA signal to form a dicistronic expression cassette. Subsequently, the dicistronic expression cassette was inserted into E1 region of Ad5 genome in cosmid vector pAx1cw of E1substitution type. By homologous recombination with EcoT22Idigested Ad5 DNATPC in 293 cells, the replicationdeficient recombinant adenoviruses of hIL12 were generated efficiently. After infected with hIL12 recombinant adenoviruses in vitro, 293 cells, human hepatocellular carcinoma cells HepG2, and primary human skin fibroblasts expressed and secreted hIL12 at comparable levels (30～60ng/ 106cells/24hr), which could stimulate the proliferation and IFNγ production of human lymphoblasts. These suggest that the dicistronic adenovirus vector of hIL12 could effectively mediate the expression of bioactive hIL12 and might be used in cancer gene therapy.
