J S Lam, G G Hillman, E Younes, E Ali, R L Maughan, E J Montecillo, J E Pontes, G P Haas
{"title":"Effect of local tumor irradiation and interleukin-2 therapy in different murine tumors.","authors":"J S Lam, G G Hillman, E Younes, E Ali, R L Maughan, E J Montecillo, J E Pontes, G P Haas","doi":"10.1097/00002371-199507000-00004","DOIUrl":"https://doi.org/10.1097/00002371-199507000-00004","url":null,"abstract":"The combined effect of local tumor irradiation and systemic immunotherapy was investigated in different murine tumors. Pulmonary metastases were induced in C57BL/6 mice by intravenous injection of MCA 205 sarcoma or B16 melanoma, and in BALB/c mice by injection of Renca renal adenocarcinoma. Local tumor irradiation was delivered to the left lung only at various doses of 300-800 cGy, followed by systemic administration of interleukin-2 (IL-2). All three tumor models responded to radiation in a dose-dependent fashion. MCA 205 and Renca tumor models were sensitive to IL-2, whereas the B16 tumor model responded poorly to IL-2 therapy. Local tumor irradiation enhanced the effects of immunotherapy in the two tumor models (MCA 205 and Renca) that responded to IL-2. These studies confirm that local tumor irradiation can greatly enhance the effectiveness of immunotherapy in a variety of tumor models, provided that the tumor is IL-2 responsive. There is further need to characterize the mechanism of the radiation-immunotherapy interaction and to initiate clinical trials to identify the variety of malignancies that may respond to this form of therapy.","PeriodicalId":79346,"journal":{"name":"Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy","volume":"18 1","pages":"28-34"},"PeriodicalIF":0.0,"publicationDate":"1995-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199507000-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19516000","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":"Unique characteristics associated with systemic adoptive immunotherapy of experimental intracerebral tumors.","authors":"J J Sussman, W L Wahl, A E Chang, S Shu","doi":"10.1097/00002371-199507000-00005","DOIUrl":"https://doi.org/10.1097/00002371-199507000-00005","url":null,"abstract":"Tumor-draining lymph node (LN) cells can be activated and expanded by stimulation with anti-CD3 followed by culture in interleukin-2 (IL-2) to acquire antitumor reactivity. Despite the lack of overt in vitro cytotoxicity, these effector cells mediate potent antitumor effects in the adoptive immunotherapy of established visceral tumors. Recently, we further demonstrated the therapeutic efficacy of anti-CD3/IL-2-activated tumor-draining LN cells for the treatment of intracerebral tumors in a neutralization assay as well as by local and systemic adoptive transfer. In this study, we analyzed the immunologic specificity, cellular requirements, and conditions that could promote the therapeutic effectiveness of the systemically transferred tumor-reactive cells. Using two antigenically distinct murine fibrosarcomas, MCA 205 and MCA 207, the adoptive immunotherapy of intracerebral tumors was immunologically specific, which was apparently determined by the tumor that stimulated the draining LN. Analysis of effector cells revealed the involvement of both CD4 + and CD8 + T cells for successful therapy. Therapeutic efficacy of the transferred cells was greatly enhanced if the tumor-bearing host was also treated with sublethal whole-body irradiation (500 cGy). However, unlike the treatment of tumors located in visceral organs, the administration of exogenous IL-2 consistently inhibited the antitumor reactivity of the transferred cells against intracerebral tumors. These results demonstrate the feasibility of treating brain tumors by systemic adoptive T-cell therapy, although the conditions for efficient treatment appear to be different from those required for visceral tumors.","PeriodicalId":79346,"journal":{"name":"Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy","volume":"18 1","pages":"35-44"},"PeriodicalIF":0.0,"publicationDate":"1995-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199507000-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19516001","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}
C Guillen, A Prieto, M Alvarez De Buergo, L Villa, H Rico, A Zea, M P Hernandez, M Alvarez-Mon
{"title":"Isradipine, a calcium-channel antagonist, has immunosuppressor activity on T lymphocytes from peripheral blood and synovial fluid from patients with autoimmune arthritis.","authors":"C Guillen, A Prieto, M Alvarez De Buergo, L Villa, H Rico, A Zea, M P Hernandez, M Alvarez-Mon","doi":"10.1097/00002371-199507000-00009","DOIUrl":"https://doi.org/10.1097/00002371-199507000-00009","url":null,"abstract":"It has been shown that calcium-channel antagonists can have an immunomodulatory effect on the activation and function of lymphocytes and that autoimmune diseases are associated with alterations in the regulation of the immune system. This study investigated the effect of a calcium-channel antagonist, isradipine, on the activation and proliferation of mononuclear cells (MNC) from the peripheral blood (PB) and synovial fluid (SF) of 41 patients with chronic autoimmune arthritis and from the PB of 16 healthy controls. Isradipine inhibits the proliferative response of these cells to mitogenic stimulation from phytohemagglutinin (PHA) and anti-CD3 monoclonal antibodies in a time- and dose-dependent manner. This inhibitory effect of isradipine on the proliferative response in the different cell preparations was not overcome by the exogenous addition of interleukin-2 to the culture medium. Additionally, isradipine inhibited MNC expression of CD25, CD71, and class II molecules of the major histocompatibility system in patients and controls after mitogenic stimulation. These results demonstrate that isradipine suppresses the activation and proliferation of MNC in PB and SF from patients with autoimmune arthritis.","PeriodicalId":79346,"journal":{"name":"Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy","volume":"18 1","pages":"66-74"},"PeriodicalIF":0.0,"publicationDate":"1995-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199507000-00009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19516005","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}
B Hennemann, C Scheibenbogen, C Schümichen, R Andreesen
{"title":"Intrahepatic adoptive immunotherapy with autologous tumorcytotoxic macrophages in patients with cancer.","authors":"B Hennemann, C Scheibenbogen, C Schümichen, R Andreesen","doi":"10.1097/00002371-199507000-00003","DOIUrl":"https://doi.org/10.1097/00002371-199507000-00003","url":null,"abstract":"Adoptive transfer of cytotoxic macrophages (MAC) may be able to correct for a defective generation of competent effector cells in patients with cancer. Here we report on a Phase I trial of adoptive transfer of autologous MAC by hepatic artery infusion in seven patients with metastatic liver disease. Clinical side effects were mild and consisted of fever and flu-like symptoms. Serum levels of C-reactive protein (CRP) increased within hours after MAC transfer and rose further in the course of repeated therapies. An increase of thrombin-anti-thrombin III complexes occurred in 31% of therapies. Serum neopterin, interleukin (IL)-6, and IL-8 did not change during therapy. In vivo tracing of 111 indium-labeled MAC revealed that on average, 43% of whole-body activity remained in the liver for 7 days. Evidence for tumor response could not be demonstrated. In conclusion, isolated liver perfusion with autologous MAC is well tolerated and induces a profound biological response in the recipient. Regional adoptive immunotherapy might be able to built up, in proximity to metastatic lesions, a potent cytotoxic cell infiltrate that could then be triggered within the patient using exogenous stimuli like endotoxin, cytokines, or other MAC activators.","PeriodicalId":79346,"journal":{"name":"Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy","volume":"18 1","pages":"19-27"},"PeriodicalIF":0.0,"publicationDate":"1995-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199507000-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19515999","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":"In situ interleukin-4 gene expression in cancer patients treated with genetically modified tumor vaccine.","authors":"Y Suminami, E M Elder, M T Lotze, T L Whiteside","doi":"10.1097/00002371-199505000-00006","DOIUrl":"https://doi.org/10.1097/00002371-199505000-00006","url":null,"abstract":"<p><p>Patients with advanced malignancies, participating in our ongoing phase I interleukin-4 (IL-4) gene therapy protocol at the Pittsburgh Cancer Institute, were vaccinated with irradiated autologous tumor cells together with IL-4 gene-transduced irradiated autologous fibroblasts. The level of expression of the IL-4 gene in cultured transduced and selected fibroblasts and in biopsies obtained from vaccination sites was evaluated using quantitative reverse transcription-polymerase chain reaction (RT-PCR). The number of copies of IL-4 mRNA/ng of total cellular RNA was determined in the transduced fibroblasts. Good agreement was observed between IL-4 message expression, as determined by RT-PCR, and IL-4 production, as determined by enzyme-linked immunosorbent assay (ELISA) in the fibroblast supernatants. Tissue biopsies of multiple vaccination sites were obtained from the patients to determine the level of gene expression in situ for IL-4 and Neo-r. The Neo-r gene was used as a marker for transduced fibroblasts. Two weeks after the first vaccination, mRNA for the IL-4 gene was still detectable in all tissue biopsies. The Neo-r gene was also detectable, indicating the presence of transduced fibroblasts in the biopsy. After the second vaccination, expression of the IL-4 and Neo-r genes was generally the highest on day 1 after vaccine administration and was considerably lower but still detectable on day 14 in all biopsies tested. These data indicate that autologous dermal fibroblasts transduced with the IL-4 and Neo-r genes and used as a source of IL-4 in tumor vaccine are able to express the IL-4 gene in vivo.</p>","PeriodicalId":79346,"journal":{"name":"Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy","volume":"17 4","pages":"238-48"},"PeriodicalIF":0.0,"publicationDate":"1995-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199505000-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18588331","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}
T J Powell, R Schreck, M McCall, T Hui, A Rice, H App, M Azam, A Ullrich, L K Shawver
{"title":"A tumor-derived protein which provides T-cell costimulation through accessory cell activation.","authors":"T J Powell, R Schreck, M McCall, T Hui, A Rice, H App, M Azam, A Ullrich, L K Shawver","doi":"10.1097/00002371-199505000-00003","DOIUrl":"https://doi.org/10.1097/00002371-199505000-00003","url":null,"abstract":"<p><p>A recently described tumor-derived glycoprotein, designated 90K, has been shown to have positive effects on the generation of cytotoxic effector cells (NK/LAK) from human PBMC. To determine the mechanism of these effects, we have examined the effects of 90K on cytokine production by human PBMC. A culture of normal PBMC with 90K alone did not result in IL-2 secretion; however, in coculture with suboptimal doses of ConA, 90K increased IL-2 secretion by PBMC. Coculture of PBMC with 90K and ConA also resulted in increased production of the cytokines IL-1, IL-6, GM-CSF, and TNF alpha. T cells depleted of accessory cells failed to respond to ConA alone, 90K alone, or the combination of ConA and 90K, suggesting that this protein does not have a direct effect on T cells. However, 90K alone was sufficient to induce cytokine production by unfractionated PBMC (IL-1, IL-6, GM-CSF, and TNF alpha) or by CD14-enriched PBMC (IL-1 and IL-6). In addition, expression of ICAM-1 was increased on a human monocytic cell line cultured with purified 90K in the absence of any other stimulus. This 90K-induced upregulation of ICAM-1 expression was accompanied by an increased accessory function of the monocytes, demonstrated by their ability to support ConA-induced activation of peripheral blood T cells. Based on the current data, we propose a model in which 90K activates accessory cells, resulting in the secretion of cytokines and the expression of adhesion molecules, which in turn act as costimulatory signals for T-cell activation. Activated T cells then produce cytokines such as IL-2, which lead to a more vigorous cell-mediated immune response to tumor cells and virus-infected cells. Thus, 90K shows promise as an immunotherapeutic reagent for diseases such as cancer and viral infection.</p>","PeriodicalId":79346,"journal":{"name":"Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy","volume":"17 4","pages":"209-21"},"PeriodicalIF":0.0,"publicationDate":"1995-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199505000-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18588328","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}
D S Gridley, D G Mackensen, J B Slater, M F Moyers, J M Slater
{"title":"Effects of proton irradiation on radiolabeled monoclonal antibody uptake in human colon tumor xenografts.","authors":"D S Gridley, D G Mackensen, J B Slater, M F Moyers, J M Slater","doi":"10.1097/00002371-199505000-00005","DOIUrl":"https://doi.org/10.1097/00002371-199505000-00005","url":null,"abstract":"<p><p>A major limitation of radiolabeled monoclonal antibodies (MAbs) for cancer imaging and therapy is their low accumulation within solid tumors. We, and others, have previously shown that pretreatment of a tumor mass with gamma radiation can increase the level of radiolabeled MAb at the tumor site. Unlike that of conventional radiation, the dose distribution of protons allows for increasing the dose to the cancer volume while reducing the normal tissue dose. The Proton Radiation Therapy Facility at LLUMC treats patients and conducts research. In this study, we sought to determine if preirradiation with proton beam can enhance the localization of radiolabeled MAb within xenotransplanted human colon tumors. T380 colon tumors, implanted s.c. into athymic mice, were subjected to proton irradiation (10 Gy, single dose) when mean tumor volume was 125-135 mm3/group. 111In-ZCE025, a murine MAb directed against carcinoembryonic antigen, was injected i.p. 2 h later, and biodistribution studies were performed 38 h thereafter. Animals irradiated with 60Co and given either 111In-ZCE025 or 111In-MOPC21, an irrelevant MAb, served as controls. The mean percentage of injected radioactivity localized within tumors was highest in the group treated with protons + 111In-ZCE025 when expressed on a per gram basis (%ID/g = 19.3). Somewhat unexpectedly, higher radioactivity was also noted in the normal tissues of these animals compared to other groups. The mean %ID/g tumor values for those given 60Co + 111In-ZCE025 or the antibody alone were 12.5 and 9.0. Our data show that preirradiation of solid tumors increases the localization of tumor-specific radiolabeled MAb at the tumor site.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":79346,"journal":{"name":"Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy","volume":"17 4","pages":"229-37"},"PeriodicalIF":0.0,"publicationDate":"1995-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199505000-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18588330","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}
D L Shawler, O Dorigo, R A Gjerset, I Royston, R E Sobol, H Fakhrai
{"title":"Comparison of gene therapy with interleukin-2 gene modified fibroblasts and tumor cells in the murine CT-26 model of colorectal carcinoma.","authors":"D L Shawler, O Dorigo, R A Gjerset, I Royston, R E Sobol, H Fakhrai","doi":"10.1097/00002371-199505000-00002","DOIUrl":"https://doi.org/10.1097/00002371-199505000-00002","url":null,"abstract":"<p><p>We compared the efficacy of gene therapy mediated by interleukin-2 (IL-2) gene-modified tumor cells to gene therapy mediated by IL-2 transduced fibroblasts in the CT-26 model of murine colorectal carcinoma. We transduced CT-26 tumor cells and BALB/c 3T3 fibroblasts with three different retroviral vectors using three different promoters for the human IL-2 gene: DC/TKIL-2 (thymidine kinase promoter), LXSN-iIL2 (long terminal repeat promoter), and LNCX-iIL2 (cytomegalovirus promoter). These transductions resulted in CT-26 and 3T3 subclones that secreted different amounts of IL-2. Immunization of animals with either CT-26/IL-2 cells or with fibroblast/IL-2 cells mixed with CT-26 induced similar levels of immunity that protected 62-82% of animals against a subsequent tumor challenge with parental CT-26. However, mice developed tumors at the site of inoculation in 46% of the animals immunized with CT-26/IL-2 cells. In a separate experiment, CT-26/IL-2 cells were exposed to 6,000 cGy of gamma irradiation to prevent tumor growth at the site of inoculation. Although the CT-26/IL-2 cells continued to secrete IL-2 after irradiation, they were no longer effective at inducing antitumor immunity. In contrast, both irradiated and nonirradiated fibroblast/IL-2 cells, mixed with irradiated CT-26, were equally effective at inducing antitumor immunity. These data suggest that in the CT-26 model, fibroblast-mediated IL-2 gene therapy has advantages for the induction of antitumor immunity and abrogation of tumorigenic potential at the site of inoculation compared with tumor cell-mediated IL-2 gene therapy.</p>","PeriodicalId":79346,"journal":{"name":"Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy","volume":"17 4","pages":"201-8"},"PeriodicalIF":0.0,"publicationDate":"1995-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199505000-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18587713","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 K Jakobsen, N P Restifo, P A Cohen, F M Marincola, L B Cheshire, W M Linehan, S A Rosenberg, R B Alexander
{"title":"Defective major histocompatibility complex class I expression in a sarcomatoid renal cell carcinoma cell line.","authors":"M K Jakobsen, N P Restifo, P A Cohen, F M Marincola, L B Cheshire, W M Linehan, S A Rosenberg, R B Alexander","doi":"10.1097/00002371-199505000-00004","DOIUrl":"https://doi.org/10.1097/00002371-199505000-00004","url":null,"abstract":"<p><p>We studied major histocompatibility complex (MHC) class I expression in 12 tumor cell culture lines established from patients with metastatic renal cell carcinoma (RCC). In one of these cell culture lines, UOK 123, we found no surface expression of beta 2-microglobulin (beta 2m) and MHC class I by flow cytometry. Immunofluorescence staining using three different monoclonal antibodies to beta 2m revealed no detectable beta 2m in the endoplasmic reticulum (ER), Golgi apparatus, cytoplasm, or on the cell surface. There was no evidence of folded class I molecules inside or on the surface of the cells; however, the ER stained intensively for unfolded class I molecules. Transient expression of beta 2m by UOK 123 after infection with a recombinant vaccinia virus containing the gene for beta 2m resulted in normal expression of both beta 2m and class I (HLA-A, B, C) determinants assessed by flow cytometry analysis. No expression of class I or beta 2m was seen with the recombinant vaccinia vector carrying a control gene. The inability of class I molecules to reach the cell surface is due to the requirement of beta 2m for proper folding and presentation of the class I MHC complex. The failure to assemble and express MHC class I complex on the cell surface renders these cells incapable of antigen presentation to cytotoxic T cells and provides a mechanism for escape from immune recognition by the tumor.</p>","PeriodicalId":79346,"journal":{"name":"Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy","volume":"17 4","pages":"222-8"},"PeriodicalIF":0.0,"publicationDate":"1995-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199505000-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18588329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y M Chen, J Whang-Peng, J M Liu, S Y Wang, C M Tsai, R P Perng
{"title":"Elevation of serum interleukin-6 levels before peak of serum granulocyte colony-stimulating factor level in chemotherapy-induced myelosuppressive patients.","authors":"Y M Chen, J Whang-Peng, J M Liu, S Y Wang, C M Tsai, R P Perng","doi":"10.1097/00002371-199505000-00007","DOIUrl":"https://doi.org/10.1097/00002371-199505000-00007","url":null,"abstract":"<p><p>The aim of this study was to ascertain whether any cytokines that function in earlier stages of hematopoiesis also fluctuate in conjunction with granulocyte colony-stimulating factor (G-CSF) in chemotherapy-induced myelosuppression. A total of seven patients were studied. All patients received 3 days of intravenous injection of combination chemotherapy. Patients' absolute neutrophil count (ANC), platelet count, serum G-CSF, interleukin-6 (IL-6), IL-3, and IL-1 alpha were monitored before chemotherapy, and then daily or every other day thereafter during the entire treatment course until the ANC returned to normal. The results showed very obvious elevation of serum IL-6 level before or concurrent with the elevation of serum G-CSF levels at the neutrophil nadir in all seven patients. The rise of IL-6 also correlated with nadir platelet levels in six of seven patients. The finding of serum IL-6 elevation was statistically significant both in neutropenic and thrombocytopenic stages. Serum IL-3 level was below minimum detectable concentrations in all seven patients. Serum IL-1 alpha was below minimum detectable concentration in six patients and demonstrated no obvious fluctuation in the remaining patient. Therefore, the present study demonstrated the chronological time sequence of cytokine fluctuation, IL-6 peak before G-CSF, in chemotherapy-induced myelosuppression. According to this finding, when cytokines are used for prevention of myelosuppression or for acceleration of its recovery, it may be logical to use a combination of cytokines in sequence, such as IL-6 initially followed by G-CSF.</p>","PeriodicalId":79346,"journal":{"name":"Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy","volume":"17 4","pages":"249-54"},"PeriodicalIF":0.0,"publicationDate":"1995-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199505000-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18588332","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}