OBJECTIVE To study the relationship between the serumlevels of IL-18 and IL-18BP in the development and growth ofprimary liver cancer,benign liver tumors and liver cirrhosis and todetermine the value of serum IL-18 an...OBJECTIVE To study the relationship between the serumlevels of IL-18 and IL-18BP in the development and growth ofprimary liver cancer,benign liver tumors and liver cirrhosis and todetermine the value of serum IL-18 and IL-18BP in the diagnosisof primary liver cancer.METHODS The serum levels of IL-18 and IL-18BP in 36 patientswith primary hepatic carcinoma(PHC)were detected.Eighteenpatients were diagnosed with various benign liver tumors and 21patients with cirrhosis of liver(LC),determined by using an ELISAassay.The serum levels of AFP in 36 patients with primary livercancer were examined.The relationship among levels of serumIL-18,IL-18BP and AFP in the primary liver cancer was explored.RESULTS The sIL-18 levels in PHC were significantly lower thanin control group,the benign liver tumor group and the LC group.The sIL-18BP in PHC was significantly higher than that in controlgroup,benign liver tumor group and LC group(P<0.001).Therewas a close correlation between the levels of IL-18,IL-18BP andclinical stage in PHC:the later clinical stages had lower levels ofIL-18 and higher levels of IL-18BP while the earlier clinical stageshad higher levels of IL-18 and lower levels of IL-18BP.There was anegative correlation between serum levels of IL-18 and AFP in thePHC group(r = -0.7152,n=36,P<0.01),and there was a positivecorrelation between serum levels of IL-18 BP and AFP in thepatients with PHC(r=0.6315,n=36,P<0.01).The IL-18 and IL-18BP in the patients with various benign liver tumors or LC weresignificantly higher than those in control group.The differenceswere statistically significant(P<0.01).CONCLUSION Serum levels of IL-18 and IL-18BP can reflectthe immune function of patients with primary liver cancer,withvarious benign liver tumors or with LC and can also be indicativeof the clinic stage of primary liver cancer.It can be used to assistin making a diagnosis and in determining the clinical stage ofPHC.Detecting AFP concurrently can help make the diagnosis ofprimary liver cancer more precise.展开更多
AIM: To identify the relationship between the tagging single nucleotide polymorphism sites (tagSNPs) of the Interleukin-18 (IL-18) gene and genetic susceptibility to chronic hepatitis B virus infection in Chinese pati...AIM: To identify the relationship between the tagging single nucleotide polymorphism sites (tagSNPs) of the Interleukin-18 (IL-18) gene and genetic susceptibility to chronic hepatitis B virus infection in Chinese patients. METHODS: Five hundred and one cases of chronic hepatitis B virus (HBV) infection and 301 HBV natural clearance controls were studied. Two tagSNPs in the IL-18 gene (rs1946518A/C and rs574424C/G) were genotyped by the Multiplex Snapshot technique. The genotype and allele frequencies were calculated and analyzed. RESULTS: In the genotypes of rs1946518, the AA type was present at a higher frequency in the patients compared to those in the controls. Odds ratio (OR) of the AA genotype for the comparison with that of the AC and the CC genotype was 1.537 (95% confidence intervals (CI): 1.116-2.218, P = 0.009 < 0.025). In phenotypes, the allele C at rs1946518 was of a significantly lower frequency in the patients with chronic hepatitis B than that in the controls (P = 0.017 < 0.025). OR of the allele A for the comparison with that of the allele C was 1.279 (95% CI: 1.045-1.567). As for the rs574424 genotypes, no significant difference in this genotype distribution or in this allele frequency between the patients and the control subjects was observed. No significant difference in the haplotype frequencies between the patients with chronic hepatitis B and HBV natural clearance individuals was displayed. CONCLUSION: The data suggest that genotype AA and the allele A of the IL-18 at position rs1946518 are closely associated with the resistance to chronic hepatitis B and may be the dangerous gene. However, no statistical association was found between polymorphisms of rs574424 for IL-18 and hepatitis B.展开更多
AIM:To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide(LPS) -induced stimulation in the liver. METHODS:Six-to-eight-week-old C57BL/6 chow fed mice were injected...AIM:To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide(LPS) -induced stimulation in the liver. METHODS:Six-to-eight-week-old C57BL/6 chow fed mice were injected intraperitoneally with 0.5μg/g bodyweight LPS and sacrificed 2,4,6,18 or 24 h later. LPS-induced liver damage was confirmed by a biochemical assay to detect alanine aminotransferase(ALT) levels.To determine if LPS stimulation in the liver led to activation of the inflammasome,real-time quantitative polymerase chain reaction was used to evaluate the mRNA expression of components of the Nalp3 inflammasome.Enzyme-linked immunosorbent assays were used to determine the protein expression levels of several downstream targets of the Nalp3 inflammasome,including caspase-1 and two cytokine targets of caspase-1,interleukin(IL) -1βand IL-18. RESULTS:We found that LPS injection resulted in liver damage as indicated by elevated ALT levels.This was associated with a significant increase in both mRNA and protein levels of the proinflammatory cy-tokine tumor necrosis factor(TNF) -αin the liver,as well as increased levels of TNFs in serum.We showed that LPS stimulation led to upregulation of mRNA levels in the liver for all the receptor components of the inflammasome,including Nalp3,Nalp1,pannexin-1 and the adaptor molecule apoptosis-associated specklike,caspase recruitment domain-domain containing protein.We also found increased levels of mRNA and protein for caspase-1,a downstream target of the inflammasome.In addition,LPS challenge led to increased levels of both mRNA and protein in the liver for two cytokine targets of caspase-1,IL-1βand IL-18. Interestingly,substantial baseline expression of pre-IL1βand pre-IL-18 was found in the liver.Inflammasome and caspase-1 activation was indicated by the significant increase in the active forms of IL-1βand IL-18 after LPS stimulation. CONCLUSION:Our results show that the Nalp3 inflammasome is upregulated and activated in the liver in response to LPS stimulation.展开更多
To analyze the antitumor potential and mechanism of action of simultaneous Newcastle disease virus (NDV) hemagglutinin-neuraminidase(HN) and human interleukin 18(hIL-18) gene transfer in C57BL/6 mice with H22 he...To analyze the antitumor potential and mechanism of action of simultaneous Newcastle disease virus (NDV) hemagglutinin-neuraminidase(HN) and human interleukin 18(hIL-18) gene transfer in C57BL/6 mice with H22 hepatoma,the mouse model with H22 hepatoma was established in C57BL/6 mice, and the antitumor effects of the combined application of NDV HN and hIL-18 were evaluated in vivo. The results show that the growth of established tumors in mice immunized with adenovirus(Ad)-HN in conjunction with Ad-hIL-18 was significantly inhibited compared with that in mice immunized with Ad-HN, Ad-hIL-18 alone, or the empty vector(Ad-mock). Furthermore, the immunization of mice with Ad-HN in conjunction with Ad-hIL-18 elicited strong natural killer activity and H22 tumor-specific cytotoxic T lymphocyte(CTL) responses in vivo. In addition, T cells from the lymph nodes of mice immunized with Ad-hIL-18 or Ad-HN+Ad-hIL-18 secreted high levels of the Th1 cytokine IL-2 and interferon-γ (IFN-γ), indicating that the regression of tumor cells is related to a Th1-type dominant immune response. These results demonstrate that vaccination with NDV HN together with hIL-18 may be a novel and powerful strategy for cancer immunotherapy.展开更多
Objective To construct the human interleukin 18 DNA plasmids vaccine and to express the eukaryotic plasmids vaccine in mammalian cell lines Cos 7 and D5.Methods Gene recombinant technique was used to construct hIL 18 ...Objective To construct the human interleukin 18 DNA plasmids vaccine and to express the eukaryotic plasmids vaccine in mammalian cell lines Cos 7 and D5.Methods Gene recombinant technique was used to construct hIL 18 eukaryotic expression vectors.Calcium phosphate method was performed to transect recombinant hIL 18 eukaryotic expression vectors into Cos 7 and D5 cells. In situ hybridization and Western Blot were implemented to verify the transient expression of recombinant hIL 18 in Cos 7 and D5.Results The eukaryotic expression plasmid pVAX1 IL 18 was constructed successfully.hIL 18 was transiently expressed in Cos 7 and D5.Conclusion The eukaryotic expression plasmid pVAX1 IL 18 was constructed. In situ hybridization and Western Blot results proved the successful transient expression of pVAX1 IL 18 in Cos 7 and D5.Therefore,the work has settled the foundation for further biological research on hIL 18,including immunogene therapy through hIL 18.展开更多
Background Epidermic studies have suggested a pathophysiological link between obstructive sleep apnea hypopnea syndrome (OSAHS) and atherosclerosis (AS); for which carotid intima-media thickness (IMT) has been c...Background Epidermic studies have suggested a pathophysiological link between obstructive sleep apnea hypopnea syndrome (OSAHS) and atherosclerosis (AS); for which carotid intima-media thickness (IMT) has been considered as an early marker. The pathogenesis by which OSAHS can induce AS has not been elucidated. This study was conducted to investigate the association among plasma interleukin-18 (IL-18) levels, carotid IMT and the severity of OSAHS. Methods Based on the apnea hypopnea index (AHI) during sleep monitored by polysomnography, 52 male patients with OSAHS were recruited as the OSAHS group which was further divided into mild OSAHS (n=16), moderate OSAHS (n=18), and severe OSAHS (n=18) subgroups. Eighteen healthy subjects were selected as the control group. Of all OSAHS patients, 20 with moderate-to-severe OSAHS underwent continuous positive airway pressure (CPAP) treatment for 90 days. HDL5000 color Doppler ultrasonography was used to measure carotid IMT. Plasma IL-18 levels were measured bv ELISA.Results Compared with the plasma IL-18 levels in the control group ((250.27±76.48) pg/ml), there was a significant increase in the mild OSAHS subgroup ((352.08±76.32) pg/ml), the moderate subgroup ((600.17±83.91) pg/ml), and the severe OSAHS subgroup ((9797.64 ± 109.83) pg/ml) (all P〈0.01). Moreover, there was a significant difference in plasma IL-18 levels among the three OSAHS subgroups (P〈0.01). Carotid IMT was significantly greater in the severe OSAHS subgroup than in the mild OSAHS subgroup (P〈0.01). Before CPAP treatment, plasma IL-18 levels were positively correlated with carotid IMT (r=0.486, P 〈0.001) and with AHI (r=0.865, P〈0.001). On day 90 of CPAP treatment, plasma IL-18 levels were significantly declined but carotid IMT was not changed significantly. Conclusions In untreated OSAHS patients carotid IMT and plasma IL-18 were positively correlated and were significantly higher than in normal controls; the elevation of plasma IL-18 levels was correlated with the severity of OSAHS. Inflammatory response associated with OSAHS may be related to the development of AS. By improving AHI, miniSaO2, and reducing plasma IL-18 levels, CPAP treatment may slow down or prevent the development of AS in OSAHS patients.展开更多
To investigate the levels of IL 18 in the bone marrow of both normal subjects a nd patients with hematological diseases and to determine the possible significan ce of IL 18 in pathogenesis of some hematological mali...To investigate the levels of IL 18 in the bone marrow of both normal subjects a nd patients with hematological diseases and to determine the possible significan ce of IL 18 in pathogenesis of some hematological malignancies Methods The IL 18 mRNA levels in the bone marrow of 140 patients with hematological dis eases and 15 normal donors were determined by the semi quantitative reverse tra nscriptase polymerase chain reaction (RT PCR) Immunohistochemical method was used to detect IL 18 protein in 12 patients with acute myeloid leukemia (AML) The possible regulation of IL 18 for proliferation of some leukemia cells was investigated using antisense techniques Results IL 18 mRNA levels were obviously higher in the patients with leukemia or other malignant hematological diseases (OMHD) than in normal donors However, no sign ificant difference was found in the level of transcription between patients with iron deficiency anemia (IDA) and normal controls Immunohistochemical method c onfirmed the presence of IL 18 protein in 10 out of 12 AML cases with positive transcription By 3 (4,5 dimethylthiazol 2 yl) 2,5 diphenyl tetrazolium b romide (MTT) assay, IL 18 antisense oligodeoxynucleotides (ASON) clearly inhibi ted the growth of J6 1 and HL 60 cells (42% and 12% inhibited, respectively) i n a dose dependant manner Conclusions IL 18 was detected at elevated levels in the bone marrow of patients with some hematological malignancies, and might be involved in the proliferation of certai n leukemic cells in vivo through an autocrine mechanism展开更多
文摘目的 :探讨烫伤后不同组织白介素 18(IL 18) m RNA的表达及其介质效应。方法 :采用大鼠 30 %体表面积 度烫伤模型 ,采用逆转录聚合酶链反应检测组织 IL 18m RNA、γ 干扰素 (IFNγ) m RNA、Fas Lm RNA含量 ,采用酶联免疫吸附 (EL ISA)法测定 IFNγ蛋白含量。结果 :烫伤后组织 IL 18m RNA表达较伤前值即有显著升高 ,8小时达高峰 ,且持续至伤后 2 4小时 ;烫伤后组织 IFNγ m RNA表达即开始增加 ,伤后 8小时达高峰。肠、肺组织 IFNγ水平与基因表达趋势基本一致。未致伤动物肠、肺可表达少量 Fas L m RNA ,烫伤可使其表达增加。相关分析表明 ,组织 IL 18m RNA表达与 IFNγ m RNA、IFNγ水平、Fas L m RNA表达均呈显著正相关。结论 :肠、肺组织 IL 18m RNA表达在烫伤早期即显著增多 ,并呈逐渐升高的趋势 ;创伤后组织 IL 18m RNA基因表达对 IFNγ、Fas L
基金supported by a grant from the Zhanjiang Municipal Scientific Research Program,China(No.Zhanke[2005]82-25).
文摘OBJECTIVE To study the relationship between the serumlevels of IL-18 and IL-18BP in the development and growth ofprimary liver cancer,benign liver tumors and liver cirrhosis and todetermine the value of serum IL-18 and IL-18BP in the diagnosisof primary liver cancer.METHODS The serum levels of IL-18 and IL-18BP in 36 patientswith primary hepatic carcinoma(PHC)were detected.Eighteenpatients were diagnosed with various benign liver tumors and 21patients with cirrhosis of liver(LC),determined by using an ELISAassay.The serum levels of AFP in 36 patients with primary livercancer were examined.The relationship among levels of serumIL-18,IL-18BP and AFP in the primary liver cancer was explored.RESULTS The sIL-18 levels in PHC were significantly lower thanin control group,the benign liver tumor group and the LC group.The sIL-18BP in PHC was significantly higher than that in controlgroup,benign liver tumor group and LC group(P<0.001).Therewas a close correlation between the levels of IL-18,IL-18BP andclinical stage in PHC:the later clinical stages had lower levels ofIL-18 and higher levels of IL-18BP while the earlier clinical stageshad higher levels of IL-18 and lower levels of IL-18BP.There was anegative correlation between serum levels of IL-18 and AFP in thePHC group(r = -0.7152,n=36,P<0.01),and there was a positivecorrelation between serum levels of IL-18 BP and AFP in thepatients with PHC(r=0.6315,n=36,P<0.01).The IL-18 and IL-18BP in the patients with various benign liver tumors or LC weresignificantly higher than those in control group.The differenceswere statistically significant(P<0.01).CONCLUSION Serum levels of IL-18 and IL-18BP can reflectthe immune function of patients with primary liver cancer,withvarious benign liver tumors or with LC and can also be indicativeof the clinic stage of primary liver cancer.It can be used to assistin making a diagnosis and in determining the clinical stage ofPHC.Detecting AFP concurrently can help make the diagnosis ofprimary liver cancer more precise.
基金Supported by the Grants from the National Natural Science Foundation of China,No.81072342the Foundation of Pre-973 Program Projects,No.2009CB526411
文摘AIM: To identify the relationship between the tagging single nucleotide polymorphism sites (tagSNPs) of the Interleukin-18 (IL-18) gene and genetic susceptibility to chronic hepatitis B virus infection in Chinese patients. METHODS: Five hundred and one cases of chronic hepatitis B virus (HBV) infection and 301 HBV natural clearance controls were studied. Two tagSNPs in the IL-18 gene (rs1946518A/C and rs574424C/G) were genotyped by the Multiplex Snapshot technique. The genotype and allele frequencies were calculated and analyzed. RESULTS: In the genotypes of rs1946518, the AA type was present at a higher frequency in the patients compared to those in the controls. Odds ratio (OR) of the AA genotype for the comparison with that of the AC and the CC genotype was 1.537 (95% confidence intervals (CI): 1.116-2.218, P = 0.009 < 0.025). In phenotypes, the allele C at rs1946518 was of a significantly lower frequency in the patients with chronic hepatitis B than that in the controls (P = 0.017 < 0.025). OR of the allele A for the comparison with that of the allele C was 1.279 (95% CI: 1.045-1.567). As for the rs574424 genotypes, no significant difference in this genotype distribution or in this allele frequency between the patients and the control subjects was observed. No significant difference in the haplotype frequencies between the patients with chronic hepatitis B and HBV natural clearance individuals was displayed. CONCLUSION: The data suggest that genotype AA and the allele A of the IL-18 at position rs1946518 are closely associated with the resistance to chronic hepatitis B and may be the dangerous gene. However, no statistical association was found between polymorphisms of rs574424 for IL-18 and hepatitis B.
文摘AIM:To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide(LPS) -induced stimulation in the liver. METHODS:Six-to-eight-week-old C57BL/6 chow fed mice were injected intraperitoneally with 0.5μg/g bodyweight LPS and sacrificed 2,4,6,18 or 24 h later. LPS-induced liver damage was confirmed by a biochemical assay to detect alanine aminotransferase(ALT) levels.To determine if LPS stimulation in the liver led to activation of the inflammasome,real-time quantitative polymerase chain reaction was used to evaluate the mRNA expression of components of the Nalp3 inflammasome.Enzyme-linked immunosorbent assays were used to determine the protein expression levels of several downstream targets of the Nalp3 inflammasome,including caspase-1 and two cytokine targets of caspase-1,interleukin(IL) -1βand IL-18. RESULTS:We found that LPS injection resulted in liver damage as indicated by elevated ALT levels.This was associated with a significant increase in both mRNA and protein levels of the proinflammatory cy-tokine tumor necrosis factor(TNF) -αin the liver,as well as increased levels of TNFs in serum.We showed that LPS stimulation led to upregulation of mRNA levels in the liver for all the receptor components of the inflammasome,including Nalp3,Nalp1,pannexin-1 and the adaptor molecule apoptosis-associated specklike,caspase recruitment domain-domain containing protein.We also found increased levels of mRNA and protein for caspase-1,a downstream target of the inflammasome.In addition,LPS challenge led to increased levels of both mRNA and protein in the liver for two cytokine targets of caspase-1,IL-1βand IL-18. Interestingly,substantial baseline expression of pre-IL1βand pre-IL-18 was found in the liver.Inflammasome and caspase-1 activation was indicated by the significant increase in the active forms of IL-1βand IL-18 after LPS stimulation. CONCLUSION:Our results show that the Nalp3 inflammasome is upregulated and activated in the liver in response to LPS stimulation.
基金Supported by the Genetically Modified Organisms Breeding Major Projects, China(No.2009ZX08006-002B)the Key Technologies Research and Development Program of Jilin Province, China(No.10ZDGG007)the Postdoctoral Science Foundation Funded Project of China(No.20100481057)
文摘To analyze the antitumor potential and mechanism of action of simultaneous Newcastle disease virus (NDV) hemagglutinin-neuraminidase(HN) and human interleukin 18(hIL-18) gene transfer in C57BL/6 mice with H22 hepatoma,the mouse model with H22 hepatoma was established in C57BL/6 mice, and the antitumor effects of the combined application of NDV HN and hIL-18 were evaluated in vivo. The results show that the growth of established tumors in mice immunized with adenovirus(Ad)-HN in conjunction with Ad-hIL-18 was significantly inhibited compared with that in mice immunized with Ad-HN, Ad-hIL-18 alone, or the empty vector(Ad-mock). Furthermore, the immunization of mice with Ad-HN in conjunction with Ad-hIL-18 elicited strong natural killer activity and H22 tumor-specific cytotoxic T lymphocyte(CTL) responses in vivo. In addition, T cells from the lymph nodes of mice immunized with Ad-hIL-18 or Ad-HN+Ad-hIL-18 secreted high levels of the Th1 cytokine IL-2 and interferon-γ (IFN-γ), indicating that the regression of tumor cells is related to a Th1-type dominant immune response. These results demonstrate that vaccination with NDV HN together with hIL-18 may be a novel and powerful strategy for cancer immunotherapy.
文摘Objective To construct the human interleukin 18 DNA plasmids vaccine and to express the eukaryotic plasmids vaccine in mammalian cell lines Cos 7 and D5.Methods Gene recombinant technique was used to construct hIL 18 eukaryotic expression vectors.Calcium phosphate method was performed to transect recombinant hIL 18 eukaryotic expression vectors into Cos 7 and D5 cells. In situ hybridization and Western Blot were implemented to verify the transient expression of recombinant hIL 18 in Cos 7 and D5.Results The eukaryotic expression plasmid pVAX1 IL 18 was constructed successfully.hIL 18 was transiently expressed in Cos 7 and D5.Conclusion The eukaryotic expression plasmid pVAX1 IL 18 was constructed. In situ hybridization and Western Blot results proved the successful transient expression of pVAX1 IL 18 in Cos 7 and D5.Therefore,the work has settled the foundation for further biological research on hIL 18,including immunogene therapy through hIL 18.
文摘Background Epidermic studies have suggested a pathophysiological link between obstructive sleep apnea hypopnea syndrome (OSAHS) and atherosclerosis (AS); for which carotid intima-media thickness (IMT) has been considered as an early marker. The pathogenesis by which OSAHS can induce AS has not been elucidated. This study was conducted to investigate the association among plasma interleukin-18 (IL-18) levels, carotid IMT and the severity of OSAHS. Methods Based on the apnea hypopnea index (AHI) during sleep monitored by polysomnography, 52 male patients with OSAHS were recruited as the OSAHS group which was further divided into mild OSAHS (n=16), moderate OSAHS (n=18), and severe OSAHS (n=18) subgroups. Eighteen healthy subjects were selected as the control group. Of all OSAHS patients, 20 with moderate-to-severe OSAHS underwent continuous positive airway pressure (CPAP) treatment for 90 days. HDL5000 color Doppler ultrasonography was used to measure carotid IMT. Plasma IL-18 levels were measured bv ELISA.Results Compared with the plasma IL-18 levels in the control group ((250.27±76.48) pg/ml), there was a significant increase in the mild OSAHS subgroup ((352.08±76.32) pg/ml), the moderate subgroup ((600.17±83.91) pg/ml), and the severe OSAHS subgroup ((9797.64 ± 109.83) pg/ml) (all P〈0.01). Moreover, there was a significant difference in plasma IL-18 levels among the three OSAHS subgroups (P〈0.01). Carotid IMT was significantly greater in the severe OSAHS subgroup than in the mild OSAHS subgroup (P〈0.01). Before CPAP treatment, plasma IL-18 levels were positively correlated with carotid IMT (r=0.486, P 〈0.001) and with AHI (r=0.865, P〈0.001). On day 90 of CPAP treatment, plasma IL-18 levels were significantly declined but carotid IMT was not changed significantly. Conclusions In untreated OSAHS patients carotid IMT and plasma IL-18 were positively correlated and were significantly higher than in normal controls; the elevation of plasma IL-18 levels was correlated with the severity of OSAHS. Inflammatory response associated with OSAHS may be related to the development of AS. By improving AHI, miniSaO2, and reducing plasma IL-18 levels, CPAP treatment may slow down or prevent the development of AS in OSAHS patients.
基金ThisworkwassupportedbytheNationalNaturalSciencesFoundationofChina (No 39980 0 1 4 )
文摘To investigate the levels of IL 18 in the bone marrow of both normal subjects a nd patients with hematological diseases and to determine the possible significan ce of IL 18 in pathogenesis of some hematological malignancies Methods The IL 18 mRNA levels in the bone marrow of 140 patients with hematological dis eases and 15 normal donors were determined by the semi quantitative reverse tra nscriptase polymerase chain reaction (RT PCR) Immunohistochemical method was used to detect IL 18 protein in 12 patients with acute myeloid leukemia (AML) The possible regulation of IL 18 for proliferation of some leukemia cells was investigated using antisense techniques Results IL 18 mRNA levels were obviously higher in the patients with leukemia or other malignant hematological diseases (OMHD) than in normal donors However, no sign ificant difference was found in the level of transcription between patients with iron deficiency anemia (IDA) and normal controls Immunohistochemical method c onfirmed the presence of IL 18 protein in 10 out of 12 AML cases with positive transcription By 3 (4,5 dimethylthiazol 2 yl) 2,5 diphenyl tetrazolium b romide (MTT) assay, IL 18 antisense oligodeoxynucleotides (ASON) clearly inhibi ted the growth of J6 1 and HL 60 cells (42% and 12% inhibited, respectively) i n a dose dependant manner Conclusions IL 18 was detected at elevated levels in the bone marrow of patients with some hematological malignancies, and might be involved in the proliferation of certai n leukemic cells in vivo through an autocrine mechanism