{"title":"Strain differences in the severity of lesions in murine systemic candidiasis correlate with the production of functional gamma interferon by Candida-activated lymphocytes in vitro.","authors":"R B Ashman, E M Bolitho","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>BALB/c mice exhibit mild, and CBA/CaH mice exhibit severe tissue lesions after systemic infection with the yeast Candida albicans. There is considerable evidence that recovery from primary infection is associated with the development of cell-mediated immune responses in the infected mice, and that cytokines produced by T lymphocytes augment the phagocytic and candidacidal functions of macrophages and polymorphonuclear leukocytes. To determine whether the severity of lesions in the two inbred strains was associated with differences in cytokine production, lymphocytes were obtained from the spleens of normal and immune mice, activated with Candida antigens in vitro, and functional cytokines identified by bioassay. mRNA obtained from the activated lymphocytes was also screened for cytokine-specific sequences by S1-nuclease protection analysis. mRNA for IL-3 and IFN-gamma, but not IL-2 or IL-4, was detected in lymphocytes from both BALB/c and CBA/CaH mice, but only lymphocytes from primary and secondary cultures of BALB/c cells showed Candida-specific induction of IFN-gamma bioactivity. These results suggest that, in this murine model of systemic candidiasis, the propensity to develop severe lesions exhibited by CBA/CaH mice may be a consequence of some form of posttranscriptional regulation of gamma-interferon production.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 6","pages":"471-6"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19117219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human granulocyte colony-stimulating factor (G-CSF), the premier granulopoietin: biology, clinical utility, and receptor structure and function.","authors":"L S Tkatch, D J Tweardy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In summary, both G-CSF and GM-CSF have been identified, cloned, and produced for pharmacologic use in humans. While both G-CSF and GM-CSF have had significant impact in the treatment of neutropenic states, G-CSF appears to be more advantageous than GM-CSF in overall efficacy and paucity of side effects. Much has been discovered about the structure of the G-CSF receptor but further work is necessary to determine its mechanism of signal transduction. As our understanding of G-CSF signaling advances, the therapeutic impact of our knowledge about G-CSF biology will evolve from the current focus on enhancing its effects in hematologic and oncologic illnesses to decreasing its effects in inflammatory conditions where overexhuberant neutrophil infiltration and activation cause disease.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 6","pages":"477-88"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18520277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M C Pagliacci, G Fumi, G Migliorati, F Grignani, C Riccardi, I Nicoletti
{"title":"Cytostatic and cytotoxic effects of tumor necrosis factor alpha on MCF-7 human breast tumor cells are differently inhibited by glucocorticoid hormones.","authors":"M C Pagliacci, G Fumi, G Migliorati, F Grignani, C Riccardi, I Nicoletti","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To investigate the mechanisms of growth inhibition exerted by TNF-alpha on tumor cells in vitro, we analyzed the cytokine effects on growth and cell-cycle parameters of cultured MCF-7 human breast cancer cells. TNF-alpha exerted a dose-dependent inhibition of MCF-7 cell growth, which reached its maximum at 1000 U/ml TNF-alpha concentrations. Flow-cytometric analysis of cell nuclei revealed two main components in TNF-alpha activity: an earlier cytostatic effect (G1/S block), was followed by nuclear shrinkage and cytolysis. The 55-60-kDa TNF-alpha receptor is involved in the growth inhibitory activity of the cytokine, since the H398 anti-55-kDa receptor antibody significantly counteracted the cytostatic and cytotoxic effects of TNF-alpha while an antibody (htr-9) with agonistic activity on the same receptor produced both cytostasis and cytolysis. Culture conditions strongly influenced the MCF-7 cell response to TNF-alpha. Serum deprivation of log-growing (i.e., high S phase percentage) cultures potentiated the cytotoxic effect, while reduction in S phase cell percentage by preculture in serum-free medium resulted in a significant inhibition of TNF-alpha action. Mitogenic hormones, such as insulin and 17 beta-estradiol+insulin, restored the sensitivity of MCF-7 cells precultured in serum-free medium to both the cytostatic and cytolytic effects of TNF-alpha. The synthetic glucocorticoid hormone dexamethasone, at micromolar concentrations, counteracted the TNF-alpha effect on MCF-7 cell growth. Flow-cytometric analysis showed that dexamethasone did not antagonize the cytostatic activity of either TNF-alpha or htr-9 agonistic antibody, but only the subsequent cytolysis.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 6","pages":"439-47"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19115866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The influence of recombinant human interleukin-6 on blood and immune parameters in middle-aged and old rhesus monkeys.","authors":"W H Sun, N Binkley, D W Bidwell, W B Ershler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>IL-6 is a 26-kDa protein cytokine with pleiotropic activities in both hematopoietic and immune systems. It is one of the major mediators of the acute phase inflammatory response. Recently it has been demonstrated that pharmacological doses of human recombinant IL-6 (rhIL-6) inhibit certain murine tumors as well as stimulate thrombopoiesis in mice, dogs, nonhuman primates, and humans. The purpose of our study was to evaluate the effects and toxicity of rhIL-6 administration in nonhuman primates with particular reference to subject age. We treated 10 female monkeys of two age groups (midle-aged and old) with rhIL-6 (15 micrograms/kg/day) for 28 days. The monkeys were observed to be somewhat lethargic and lost an average of 10% of their body weights. The white blood cell count rose transiently whereas the levels of hemoglobin and hematocrit fell significantly and remained depressed for the same period. Importantly, platelet count rose and remained elevated for the duration of treatments. Serum alkaline phosphatase levels increase significantly and certain parameters of clinical immune competence were altered by IL-6 treatment. Treatment effects were similar in both age groups, but the changes in immune functions were different between the midle-aged and old monkeys. We observed a pattern in which the middle-aged group had a significant decrease in immune functions as a result of IL-6 administration and recovered to pretreatment level despite continuous treatment, whereas the old monkeys had a more protracted but less significant decline in these same immune functions during the trial.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 6","pages":"449-55"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19115869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y Abe, M Van Eden, M Gatanaga, F I Wang, H D Brightbill, G A Granger, T Gatanaga
{"title":"The role of lymphotoxin in the IL-2-driven differentiation of human lymphokine-activated T-killer (T-LAK) cells in vitro.","authors":"Y Abe, M Van Eden, M Gatanaga, F I Wang, H D Brightbill, G A Granger, T Gatanaga","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Brief stimulation of human peripheral blood mononuclear cells with PHA and subsequent coculture with IL-2 results by 5 days in cultures of human lymphokine-activated killer (T-LAK) cells. While IL-2 drives the proliferation of these cells in vitro, their maturation into functional effector cells capable of cytokine secretion and cell cytokines depends on the presence of other cytokines. The role of LT in the differentiation and proliferation of human T-LAK cells in vitro was investigated. Higher levels of LT than TNF were secreted by T-LAK cells during the first 5 days of the primary culture, then secretion levels dropped sharply. Human T-LAK cells cultivated with anti-LT rabbit antisera showed a slight reduction in growth compared to normal rabbit serum controls. In contrast, phenotypic analysis by FACS showed a decrease in CD4+ and an increase in CD8+ populations of T-LAK cells in the treated cultures. Addition of LT from the beginning of the T-LAK cell culture resulted in an increase in CD4+ and a decrease in CD8+ cell populations at day 7. In addition, the cytolytic activity of non-MHC-restricted cytotoxicity and NK-like activity of anti-LT cultured T-LAK cells was also effected. These data indicated that LT may have a role in differentiation of IL-2 stimulated human T-LAK cells in vitro.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 5","pages":"279-83"},"PeriodicalIF":0.0,"publicationDate":"1993-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19248840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The CD4 surface antigen is induced and maintained on a T-lymphoid cell line by tumor necrosis factor-alpha.","authors":"B K Brightman, H Fan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have used the L4E murine thymoma-derived T-lymphoid cell line to study mechanisms involved in CD4 expression. When L4E cells are cocultured with the St3 stromal cell line, surface CD4 expression is maintained, even across a membrane. However, when transferred to medium alone, these cells rapidly lose CD4. We have tested whether CD4 can be maintained on CD4+ L4E cells when they are transferred to medium containing known cytokines. In these results, rmTNF-alpha maintained surface CD4 expression at significant levels on L4E cells. In addition, rmTNF-alpha could induce CD4 on CD4- L4E cells (obtained by growth in medium alone). Despite these results CD4 induction and maintenance in L4E cells by coculture with St3 stroma did not appear to result from secretion of TNF-alpha, since St3 cells did not express TNF-alpha mRNA, secreted TNF-alpha was not detected by ELISA assay in supernatant from St3 cells nor L4E-St3 cocultures, and incubation with neutralizing anti-TNF-alpha antibody did not inhibit CD4 maintenance. The ability of TNF-alpha to affect CD4 expression on L4E cells supports a role in thymocyte differentiation for this cytokine.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 5","pages":"293-302"},"PeriodicalIF":0.0,"publicationDate":"1993-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19248842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulation of M-CSF production by cultured human thymic epithelial cells.","authors":"A H Galy, H Spits, J A Hamilton","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have studied the regulation of M-CSF production by human thymic epithelial cells (TEC) in a continuing effort to better understand the contribution of TEC to the intrathymic cytokine network. The levels of M-CSF were measured by radioimmunoassay. Five different TEC cultures were studied and we found that all cells examined produced M-CSF constitutively. We also studied the effects of cytokines on the regulation of the M-CSF secretion profile. IL-1, which strongly induces the secretion of a number of cytokines in TEC, was found to up-regulate M-CSF levels. The effects of IL-1 were dose and time dependent suggesting a direct effect on TEC. IFN-gamma is known to up-regulate cell surface antigens, and to modulate the IL-1-induced cytokine response in TEC. IFN-gamma could induce M-CSF by itself, but the effects were less pronounced than those of IL-1. IFN-gamma did not modify the IL-1-induced M-CSF. IL-4, which has been shown to partially modulate the IL-1-induced GM-CSF in TEC, had no effect on constitutive or induced M-CSF levels. These data are discussed in the context of the regulation of myelopoietic growth factor production by thymic stromal cells.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 5","pages":"265-70"},"PeriodicalIF":0.0,"publicationDate":"1993-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19249578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lymphokines and Cytokines, from Clone to Clinic, 1993. Combined meeting of the 8th International Lymphokine Workshop and the 4th International Workshop on Cytokines. Osaka, Japan, October 17-21, 1993. Program and Abstracts.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 5","pages":"313-419"},"PeriodicalIF":0.0,"publicationDate":"1993-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18900560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cytotoxicity and manganese superoxide dismutase induction by tumor necrosis factor-alpha and ionizing radiation in MCF-7 human breast carcinoma cells.","authors":"P S Lin, K C Ho, S J Sung, S Tsai","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Both tumor necrosis factor-alpha (TNF) and ionizing radiation cause active-oxygen radical-mediated cell injuries and cell death. Thus cells treated by both TNF and radiation may suffer greater injuries than cells treated by either agent alone. On the other hand, TNF or radiation treatment can stimulate the expression of a mitochondrial superoxide scavenging enzyme, manganese superoxide dismutase (MnSOD), which can lower the cytotoxic effects of both agents. Thus, the induction of MnSOD by radiation may interfere with the cytotoxic action of TNF and vice versa. We used a human breast tumor cell line, MCF-7, to determine the interaction of TNF and radiation on cytotoxicity and MnSOD expression. TNF was found to be more effective as a cytotoxic agent when used before than after radiation treatment. These observations suggest that radiation induced-MnSOD was more effective in reducing the cytotoxic effect of TNF whereas TNF induction of MnSOD was less effective in counteracting the radiation action. Our results not only underscore the different effects of the treatment order of TNF and radiation, but also point to potential implication in the radiotherapy of breast tumors.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 5","pages":"303-8"},"PeriodicalIF":0.0,"publicationDate":"1993-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19248843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synergism between human recombinant monocyte chemotactic and activating factor and lipopolysaccharide for activation of antitumor properties in human blood monocytes.","authors":"R K Singh, I J Fidler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Monocyte chemotactic and activating factor (MCAF) is an important mediator of monocyte recruitment to sites of chronic inflammation and neoplasia. In the present study, we determined whether MCAF can also enhance the activation of tumoricidal capacity of monocytes. Human monocytes incubated with MCAF and subthreshold concentrations of lipopolysaccharide (LPS) exhibited synergistic tumoricidal activity against allogeneic A375 melanoma cells, irrespective of their metastatic potential. The sequence of MCAF and LPS treatment was crucial. Monocytes treated first with MCAF for 4 h and then with LPS for 18 h were highly cytotoxic to the melanoma cells, whereas monocytes first treated with LPS and then with MCAF were not. Treatment of monocytes with MCAF and LPS also significantly increased production of tumor necrosis factor. These data suggest that like interferon-gamma, MCAF can prime human monocytes to respond to LPS. Interleukin-8, a chemokine for neutrophils, did not enhance the monocytes' LPS-triggered tumoricidal response. Collectively, these data show that MCAF can influence the recruitment and tumoricidal activation of blood monocytes. Therefore, MCAF may be an important mediator of tumor regression.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 5","pages":"285-91"},"PeriodicalIF":0.0,"publicationDate":"1993-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19248841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}