{"title":"Dysregulation of inflammatory cytokines in unrelated bone marrow transplantation.","authors":"A Nagler, A Bishara, C Brautbar, V Barak","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The dysregulation of cytokines is thought to play a role in the inflammatory and allospecific components of graft-versus-host disease (GVHD) and graft rejection (GR) post allogeneic bone marrow transplantation (BMT). Both complications occur post unrelated BMT at significantly higher frequencies than post BMT from identical sibling donors. The levels of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta, IL-6, IL-10 and IL-12 following unrelated BMT were measured to examine cytokine dysregulation involvement in GVHD and GR. Of the 26 patients included in this study, 15 developed GVHD (14 acute; 1 acute and chronic), 5 had GR and 6 had uneventful BMT. TNF-alpha was markedly elevated in 13/15 of the patients with GVHD and in 3/5 patients with GR. IL-6 was elevated in patients with acute GVHD and with GR. IL-12 levels were similar in pre- and post-BMT sera. No correlation was found between HLA-C match and cytokine levels. In conclusion, a positive correlation was found between elevated levels of TNF-alpha, IL-6 and IL-10, and GVHD (p < 0.05, p < 0.005 and p < 0.002 respectively) and GR (p < 0.01).</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 3","pages":"161-7"},"PeriodicalIF":0.0,"publicationDate":"1998-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20737337","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":"Expression of the human GM-CSF receptor alpha subunit in Saccharomyces cerevisiae.","authors":"J Tu, D W Golde, J C Vera, M L Heaney","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The alpha subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a 45 kDa membrane protein with a higher apparent molecular weight of 50-85 kDa due to glycosylation. Previously, we had demonstrated that N-glycosylation plays a critical role in the GM-CSF receptor-ligand interaction. To assess the activity of the alpha subunit of the human GM-CSF receptor (GMRalpha) in a lower eukaryote, we expressed GMRalpha in the yeast S. cerevisiae and found that the protein has a lower apparent molecular weight compared with that expressed in mammalian cells. Using indirect immunofluorescence microscopy, we showed that GMRalpha protein expressed in yeast localizes to the plasma membrane. Although the yeast-expressed GMRalpha is able to interact with anti-GMRalpha antibody, the heterologously expressed receptor does not bind GM-CSF. Our results indicate that specific sites and/or forms of glycosylation of the GM-CSF receptor are crucial for ligand binding.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 3","pages":"147-51"},"PeriodicalIF":0.0,"publicationDate":"1998-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20737335","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}
S Revelli, G Didoli, E Roggero, H Moreno, J Bernabo, J Wietzerbin, O Bottasso
{"title":"Macrophage activity, IL-6 levels, antibody response and heart histology in rats undergoing an attenuated Trypanosoma cruzi acute infection upon treatment with recombinant interferon gamma.","authors":"S Revelli, G Didoli, E Roggero, H Moreno, J Bernabo, J Wietzerbin, O Bottasso","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Earlier experiments in Trypanosoma cruzi-infected rats showed that recombinant rat (Rr) interferon (IFN)-gamma given shortly after infection ameliorated acute disease without modifying the serum titers of endogenously synthesized IFN-gamma and tumor necrosis factor. To gain some insight into the processes underlying this protective effect, 21-day old 'I' rats that were infected with T. cruzi and the following day started with a 20-day cycle of RrIFN-gamma injections (20000 IU/rat/day) were investigated for the in vitro replication of T. cruzi and nitric oxide (NO) production by peritoneal macrophages (day 7 post-infection, pi), antibodies with lytic activity against T. cruzi (days 7, 20, and 28 pi), and serum levels of biologically active interleukin (IL)-6 (days 15 and 30 pi). Therapy with RrIFN-gamma rendered cultured peritoneal macrophages less permissive to infection with T. cruzi. Such an effect was not accompanied by higher amounts of NO in macrophage cultured supernatants, compared with those from T. cruzi-infected rats receiving no RrIFN-gamma, which appeared not to be protected from in vitro infection. Acutely T. cruzi-infected rats had significant amounts of IL-6 in their sera - this not being the case in infected rats given RrIFN-gamma, whose levels appeared decreased as in control rats. The presence of complement-mediated anti-T. cruzi lytic antibodies was not modified by RrIFN-gamma. Likewise, heart histology at day 7 pi revealed that treatment with RrIFN-gamma made no differences as to the amount of acute inflammation, but tended to reduce the myocardial parasite load.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 3","pages":"153-9"},"PeriodicalIF":0.0,"publicationDate":"1998-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20737336","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 implications of granulocyte-monocyte colony-stimulating factor (GM-CSF) in cytotoxicity of bone marrow transplantation.","authors":"A Toren, A Nagler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>One of the major obstacles to the successful outcome of autologous bone marrow transplantation (ABMT) is the high relapse rate, which is most likely due to the lack of a graft-versus-tumor effect. The amplification of cell-mediated effector mechanisms against residual tumor cells is one of the ways to reduce relapse rates post ABMT at the stage of minimal residual disease. Granulocyte-monocyte colony-stimulating factor (GM-CSF) is a key cytokine that plays a major role in cytotoxicity and in the activation pathways of monocytes, macrophages, dendritic cells and tumor-infiltrating lymphocytes. Therefore it may be used for manipulating the immune system to fight against cancer. The activities of GM-CSF on monocytes-macrophages, dendritic cells and recruited components of the immune system are described in the context of the development of improved strategies for conferring enhanced resistance to a tumor-bearing host following autologous or allogeneic bone marrow transplants.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 3","pages":"199-206"},"PeriodicalIF":0.0,"publicationDate":"1998-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20737223","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":"Role of cytokines in the maintenance of the memory immune response induced by a rat histiocytoma in syngeneic hosts.","authors":"K S Nandakumar, C Varalakshmi, A Khar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The nature of immune memory induced by a rat histiocytoma, AK-5, in syngeneic hosts was studied. AK-5 tumor when transplanted intraperitoneally (i.p.) into naive animals grows as ascites and is 100% fatal. However, spontaneous regression of AK-5 tumor was observed in 60% of animals upon s.c. transplantation. Interestingly, all the tumor-rejected animals (immune) were found to resist further i.p. challenges with AK-5 cells. The immunity thus developed is specific for AK-5 tumor, since other tumors grow in these animals. In order to understand the tumor-specific immune memory induced after AK-5 tumor transplantation, we have evaluated circulatory-cytokine profiles of i.p. tumor-transplanted naive and immune animals. Our results show an increase in the levels of IL-2, IL-12 and IL-4 in tumor-injected immune animals compared with normal animals, whereas the interferon-gamma levels were totally reversed in these two sets of animals. We also found elevated levels of circulating immune complexes in the sera from AK-5-rechallenged immune animals. We have also evaluated the cytotoxic potential of splenocytes and pure natural killer cells from immune animals rechallenged with AK-5 cells, and have found a significant increase in antibody-dependent cellular cytotoxicity. Similarly, in vitro proliferation of total splenocytes and nylon-wool non-adherent cells from immune animals was much higher compared with the normal animals. The present study thus suggests antigen-independent maintenance of clonal burst size, which could be the form of immune memory induced by AK-5 tumor in the syngeneic host.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 3","pages":"169-75"},"PeriodicalIF":0.0,"publicationDate":"1998-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20737338","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":"Techniques for quantification of cytokine mRNAs.","authors":"O Benveniste, M Martin, F Villinger, D Dormont","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Various methods are currently used to monitor cytokine mRNA expression levels in clinical samples. In instances where sample size is limited (e.g. biopsies), amplification procedures such as reverse transcription followed by polymerase chain reaction amplification appear to be the only ones that are currently useful. This paper provides a review of such techniques for the detection and quantitation of cytokine message in clinical samples, and compares semiquantitative and competitive techniques in terms of sensitivity, reproducibility, feasibility and costs.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 3","pages":"207-14"},"PeriodicalIF":0.0,"publicationDate":"1998-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20737224","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":"G-CSF production in human bladder cancer and its ability to promote autocrine growth: a review.","authors":"M Tachibana, M Murai","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A variety of non-hematopoietic malignant tumors have been demonstrated to secrete granulocyte colony-stimulating factor (G-CSF) in amounts large enough to cause a significant systemic hematopoietic effect. Meanwhile, bladder cancer cells have been shown to secrete a variety of biological factors with no direct relation to urothelial cell origin. G-CSF produced by non-hematopoietic malignant cells in particular has been reported to be capable of inducing a leukemoid reaction in the host through intense stimulation of leukocyte production. This is most frequently associated with aggressive tumor cell growth and a poor clinical outcome. On the other hand, receptors for G-CSF have also been found on the cell surfaces of several non-hematopoietic cell types. These observations lead naturally to the tempting speculation that simultaneous acquisition of the ligand promotion and its receptor expression by a malignant tumor may provide a strong autocrine growth advantage. However, the role of autocrine growth factors in malignancy is even less clear, although it is undoubtedly important. In this review, G-CSF and tumor cell growth, particularly of human transitional cell carcinomas of the bladder, are discussed, and autocrine growth of human solid tumors is also summarized.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 2","pages":"113-20"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20597933","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":"Cytokine gene transduction into non-immunogeneic murine tumor cells.","authors":"S Morecki, A Lubina-Salomon, S Slavin, A Nagler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effect of cytokine transduction on the tumorigenicity and immunogenicity of murine non-immunogeneic mammary carcinoma (4T1), acute myeloid leukemia (mAML) and partially immunogenic B-cell leukemia (BCL1) has been evaluated in syngeneic strains of mice. Transduction by retroviral vectors containing the genes for GM-CSF, IL-2 or IFN-gamma did not lead to a marked antitumor effect in 4T1 mammary tumor or BCL1. A reduced local tumor size was observed in mice inoculated with 4T1 cells transduced with both GM-CSF and IL-2 genes followed by an in vitro exposure to recombinant IFN-gamma, but survival was not prolonged. Tumorigenicity of mAML cells transduced with the gene coding for IFN-gamma was significantly reduced as manifested by prolonged survival of mice in comparison with animals inoculated with non-transduced mAML cells. Transduction by each of the aforementioned cytokines did not affect the immunogenicity of these tumor model cells. The results suggest that genetic modification of spontaneous and non-immunogenic experimental tumor models does not necessarily support direct utilization of cytokine gene therapy for clinical application. More effective methods have yet to be established in order to achieve an antitumor effect in spontaneous non-immunogenic malignancies.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 2","pages":"87-94"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20598599","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":"G-CSF production in human bladder cancer and its ability to promote autocrine growth: a review.","authors":"M. Tachibana, M. Murai","doi":"10.1016/S0022-5347(05)68641-7","DOIUrl":"https://doi.org/10.1016/S0022-5347(05)68641-7","url":null,"abstract":"","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 2 1","pages":"113-20"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0022-5347(05)68641-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55684234","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}
R S Freedman, R Lenzi, A P Kudelka, D D Lawrence, M Rosenblum, C D Platsoucas
{"title":"Intraperitoneal immunotherapy of peritoneal carcinomatosis.","authors":"R S Freedman, R Lenzi, A P Kudelka, D D Lawrence, M Rosenblum, C D Platsoucas","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Carcinomas that originate in the ovary or from different sites in the gastrointestinal tract frequently develop metastases that involve the peritoneal and serosal surfaces. Carcinomatous involvement of the peritoneum is a significant cause of morbidity and mortality. Advances in our understanding of the immunobiology of the peritoneal cavity and the availability of technically advanced immunotherapeutic agents are providing an important opportunity for the intraperitoneal delivery of these agents. This review describes newer concepts in tumor immunology that have a bearing on the further development of intraperitoneal immunotherapy; delivery systems for and issues to be resolved in intraperitoneal immunotherapy, and results of studies with recombinant interferons alpha and gamma and interleukin (IL)-2, cellular therapies including lymphokine-activated killer cells, tumor-infiltrating lymphocytes, monoclonal antibodies, and intraperitoneal radioimmunotherapy. New trials of intraperitoneal immunotherapy employing novel agents, including IL-12 and genetically modified tumor vaccines, are discussed, as are issues related to the integration of immunotherapy with standard chemotherapy agents. A number of immunotherapy agents have been tested intraperitoneally and have shown promising clinical activity with acceptable toxicity. Complete responses have been documented at surgical restaging, and intraperitoneal treatments with these agents may soon be included in the therapeutic armamentarium for patients with peritoneal carcinomatosis.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 2","pages":"121-40"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20597934","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}