Activity of growth factors in the IL-6 group in the differentiation of human lung adenocarcinoma

The role of the interleukin-6 (IL-6) group of cytokines in differentiation of two lung adenocarcinoma cell lines has been examined using induction of alkaline phosphatase and expression of surfactant protein A. Oncostatin M was the most active and potent for alkaline phosphatase in A549 cells, with IL-6 having similar activity but less potency. Neither cytokine induced alkaline phosphatase in NCI-H441 cells, although induction was obtained with lung fibroblast-conditioned medium. Surfactant protein A was induced in NCI-H441 cells by conditioned medium and dexamethasone and, to a much lesser extent, by oncostatin M or IL-6. Induction of alkaline phosphatase and surfactant protein A were both dexamethasone-dependent, though some induction of surfactant protein A was obtained with interferon-alpha in the absence of dexamethasone. The activity present in lung fibroblast-conditioned medium suggests paracrine control, but this appears not to be due to oncostatin M or IL-6 as disabling antibodies to either cytokine were not inhibitory, and, although alkaline phosphatase was induced in A549 by both cytokines, it was only induced by conditioned medium in NCI-H441 cells. Furthermore, surfactant protein A was induced in H441 by conditioned medium to a much greater extent than by oncostatin M or IL-6. These data demonstrate that cytokines of the IL-6 group have potential as differentiation inducers in lung adenocarcinoma cells and that there is an equivalent paracrine factor(s) in lung fibroblast conditioned medium. As the production of this factor by fibroblasts is not enhanced by glucocorticoid, although the response of the target cell is, it would appear to be distinct from the fibrocyte pneumocyte factor previously described by Post et al 1984.     

Effect of a fluorinated pyrimidine on cachexia and tumour growth in murine cachexia models: relationship with a proteolysis inducing factor

The fluorinated pyrimidine nucleoside, 5'-deoxy-5-fluorouridine (5'-dFUrd) has been shown to effectively attenuate the progress of cachexia in the murine adenocarcinomas MAC16 and colon 26 as well as in the human uterine cervical carcinoma xenograft, Yumoto. Although concomitant inhibition of tumour growth was observed in all three models this was not sufficient to account for the preservation of body weight. An attempt has been made to correlate the anti-cachectic activity of 5'-dFUrd with the presence of a tumour produced proteolysis-inducing factor (PIF), thought to be responsible for the development of cachexia in the MAC16 model. Two variants of colon 26 adenocarcinoma were employed, clone 20 which produces profound cachexia, and clone 5 which produces no change in body weight in recipient animals. Mice bearing the colon 26, clone 20 variant showed evidence for the presence of PIF in tumour, serum and urine, while there was no evidence for the presence of PIF in tumour or body fluids of mice bearing the clone 5 tumours. Treatment of animals bearing the clone 20 variant with 5'-dF Urd led to the disappearance of PIF from the tumour, serum and urine concomitant with the attenuation of the development of cachexia. The human cervical carcinoma, Yumoto, which also induced cachexia in recipiant animals, showed expression of PIF in tumour, serum and urine in control and vehicle-treated mice, but was absent in mice treated with 5'-dFUrd. Thus in these experimental models cachexia appears to be correlated with the presence of PIF.     

系统性红斑狼疮患者外周血淋巴细胞增殖功能及其产生白细胞 …

目的 研究系统性红斑狼疮（ＳＬＥ）患才吉淋巴细胞（ＰＢＬ）增殖反应及其产生白细胞介素２（ＩＬ－２）的情况。方法 淋巴细胞增殖法及ＩＬ－２检测法,结果 ＳＬＥ患者ＰＢＬ的增殖反应明显高于正常人,但ＳＬＥ患者ＰＢＬ产生ＩＬ－２的能力明显低于正常人。结论 ＳＬＥ患者ＰＢＬ增殖反应提高和其产生ＩＬ－２能力降低可能与Ｔ细胞两亚群ＴＨ１／ＴＨ２的失衡有关。     

Infiltrating dendritic/Langerhans cells in primary breast cancer

It is fully anticipated that dendritic cells (DCs) will become a mainstay for inclusion in biological therapies for patients with cancer including breast cancer. To elucidate the cellular composition of DCs infiltrating human breast cancers, we investigated the correlations between the density of infiltrating DCs and some clinicopathological factors of breast cancer patients, examined cytokine expression on cancer cells and finally, assessed the numbers of CD45RO⁺ tumor infiltrating lymphocytes (TIL). Tissues adjacent to cancer nests contained significantly more S-100 protein⁺ and S-100 protein⁺ CD1a^– DCs, but less CD1a⁺ DCs, than the nests. In invasive ductal carcinomas infiltration by S-100 protein⁺ DCs within and adjacent to nests, CDla⁺ DCs within nests and S-100 protein⁺ CD1a^– DCs adjacent to nests was denser than that in non-invasive carcinomas. With respect to the histological subtypes, there were fewer DCs in scirrhous carcinomas. Patients with stage IV disease had significantly fewer DCs of primary lesions than at other clinical stages. There were good correlations between infiltration by S-100 protein⁺ DCs and expression of the cytokines GM-CSF, IL-1 and TNF- on cancer cells and between GM-CSF expression and S-100 protein⁺ CD1a^– DCs. There was a close correlation between CD45RO⁺ TIL and S-100 protein⁺ DC densities both within and adjacent to the cancer nests and the S-100 protein⁺ CD1a^– DC density adjacent to the cancer nests. Despite extensive immunoelectron microscopic observation, CD1a⁺ DCs within cancer nests contained only few Birbeck's granule-like structure. These data indicate that cancer nests are infiltrated predominantly by CD1a⁺ DCs, whereas S-100 protein⁺ CD1a^– DCs predominate in surrounding tissues, and a infiltration by DCs may require cytokine expression on cancer cells and simultaneous lymphocyte infiltration. The findings of this clinicopathological study indicate the importance of evaluating simultaneously the types and localizations of infiltrating DCs in cancer tissues.     

冠心病与IL-10,IL-4和IFN-γ浓度关系的研究

目的研究冠心病患者血清白细胞介素-10(IL-10)、白细胞介素-4(IL-4)、γ干扰素(IFN-γ)浓度变化及其对冠心病发病的影响。方法选取非冠心病组28人,按相同性别、年龄配对原则,通过冠脉造影选取冠心病患者28人。用放射免疫法检测两组血清IL-10t和IL-4浓度;酶联免疫吸附法检测两组血清IFN-γ浓度。结果两组IL-10浓度差异无统计学意义(P>0.05);冠心病组较对照组IL-4浓度增高(P<0.05);冠心病组较对照组IFN-γ浓度明显增高(P<0.01);Logistic回归显示IL-4及IFN-γ对冠心病发病的影响有统计学意义(均为P<0.05)。结论内源性IL-10不足以阻止冠心病的发生、发展;IFN-γ和IL-4促进冠心病的发生、发展。     

慢性前列腺炎患者前列腺液IL-1β和TNF-α的检测及意义

目的 :了解IL 1β和TNF α在慢性前列腺炎患者前列腺按摩液 (EPS)中的变化及临床意义。 　方法 :应用ELISA法对 34例慢性前列腺炎 [EPS中白细胞 (WBC)计数≥ 10 /HP为A组 16例 ,WBC <10 /HP为B组 18例 ]、10例无症状性前列腺炎、12例良性前列腺增生 (BPH)及 8例健康对照EPS中的IL 1β和TNF α进行检测。 　结果 :IL 1β和TNF α在EPS中WBC≥ 10 /HP的慢性前列腺炎和无症状性前列腺炎两组检测值明显高于WBC <10 /HP的慢性前列腺炎、BPH和健康对照 3组 (P <0 .0 5 ,P <0 .0 2 )。IL 1β与TNF α有显著的数列等级相关性 (P <0 .0 0 3) ,而WBC计数和IL 1β、TNF α之间的数列等级相关性无显著性意义。 　结论 :IL 1β与TNF α在伴有WBC计数增高的慢性前列腺炎患者EPS中明显增高 ,IL 1β与TNF α对传统以WBC计数为慢性前列腺炎进行分类的方法可以提供一个更准确的新分类方法。     

The expression of the EBV latent membrane protein (LMP-1) is independent of CD23 and bcl-2 in Reed-Sternberg cells in Hodgkin''s disease

A series of 33 cases of Hodgkin's disease was investigated for the presence of the EBV encoded latent gene product LMP-1 and of CD23 using immunohistochemical techniques. The expression of bcl-2 was examined in a subset of cases. LMP-1 was detected in the Reed-Sternberg cells in 15 cases. Although LMP-1 is known to upregulate CD23 and bcl-2, there was no correlation between the expression of LMP-1 and the detection of CD23 and bcl-2 in Reed-Sternberg cells.     

Mode of release of interleukin-8 from proliferating human epidermal keratinocytes in vitro

Abstract Keratinocytes have been shown to express interleukin-8 (IL-8) mRNA on stimulation with IL-1 and other substances. This has been assumed to account for the large amount of this neutrophil chemotaclic cytokine in psoriasis. We found that, without any added agents, commercially available normal human epidermal keratinocytes proliferating in Keratinocyte Growth Medium® (KGM) released a chemotactic peptide extracellularly, which was confirmed to be IL-8. To determine whether most of the IL-8 is secreted extracellularly from proliferating keratinocytes or is mainly stored to be released only on stimulation. We quantified cell-associated and released immunoreactive IL-8 from keratinocytes cultured in KGM for up to 11 days at the peptide level. The keratinocytes proliferated, taking a sigmoid growth curve, to reach a plateau at day 7. We found that the amounts of immunoreactive IL-8 gradually increased in the culture supernatant with cell growth but its prominent release took place only after the cell growth reached a plateau. The cell-associated IL-8 was much smaller in amount than that noted in the supernatant. These results suggest that the IL-8 constitutively produced by keratinocytes was mostly released extracellularly but that the production by actively proliferating cells seems to be far less than that by non-proliferating cells that probably occurred in an autocrine fashion under the stimulation of keratinocyte-derived cytokines accumulated in the culture medium. Neutrophil chemotactic activity assayed concomitantly showed a consistent increase during the culture period, indicating that, with their growth, the keratinocytes release substances other than IL-8 that exert an influence on neutrophil chemotactic functions.     

Effects of interleukin-12 on natural killer cell cytotoxicity and the production of interferon-7 and tumour necrosis factor-a in patients with myelodysplastic syndromes

The effects of Interleukin 12 (IL-12) on natural killer (NK) cell cytotoxicity and on the production of interferon-7 (IFN-7) and tumour necrosis factor-a (TNF-a) were examined in 15 patients with myelodysplastic syndromes (MDS), which are well known to have immunologic defects, and in 11 normal subjects. The NK cell cytotoxicity of all of the normal subjects was augmented by incubation with IL-12 alone, and co-incubation with interleukin 2 (IL-2) further augmented it (type A response). The MDS patients showed varied responses to IL-12/IL-2. Seven patients showed the type A response, resulting in augmented NK cell cytotoxicity which was similar to that in the normal subjects. In five other patients the cytotoxicity was not increased by IL-12 alone, but the combination of IL-12 and IL-2 did augment the cytotoxicity (type B response). The augmented cytotoxicity in these type B patients was lower than that in the normal subjects. In the final three MDS patients the cytotoxicity was low and not affected by IL- 12 and/or IL-2 (type C response). AH patients with refractory anaemia with excess blasts (RAEB) and patients with RAEB in transformation showed a type B or C response. Conversely, six of eight refractory anaemia patients showed a type A response. In MDS patients there was a positive correlation between the percentage of CD3CD56⁺ cells in pre-incubated cells and the cytotoxicity of cells incubated with IL-12/IL-2. The combination of IL-12 and IL-2 augmented IFN-7 and TNF-Q production by nonadherent mononuclear cells in a synergistic or cumulative manner, respectively, in most patients. These results suggest that IL-12, alone or with IL-2, may modulate these important immunologic functions in most MDS patients.     

Severe chronic active giftein-Barr virus infection accompanied by virus-associated hemophagocytic syndrome,cerebellar ataxia and encephalitis

We present a rare case of chronic active giftein-Barr virus (EBV) infection showing various clinical outcomes. A 26-year-old man was admitted to our hospital due to persistent fever and dyspnea. Serologic response of the patient to EBV indicated chronic active infection. He showed pleuritis, parotitis, chronic hepatic dysfunction, disseminated intravascular coagulation, virus associated hemophaghocytic syndrome, acute rhabdomyolysis, acute renal failure, acute cerebellar ataxia, encephalitis and multiple brain abscesses. None of acyclovir, gancyclovir, prednisolone or interleukin-2 was effectual to abolish those abnormalities. This is the first report of transient cerebellar ataxia which aggravated to panencephalitis associated with chronic EBV infection.