ISSN:0732-6580    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Summary:Treatment with human recombinant interleukin‐2 (rIL‐2) is associated with multiple organ dysfunctions, including hepatic and cardiac toxicities. We present a rabbit model that may be highly suited to investigations of these organ toxicities. Rabbits were treated with rIL‐2 at a dose of 3 × 106Cetus units/kg/day in divided doses every 8 h for 9‐11 doses. Control animals received either excipient or 5% dextrose in water. Treatment with rIL‐2 resulted in hepatic and myocardial infiltration by lymphocytes and mononuclear cells. Monoclonal antibody‐staining techniques revealed a high percentage of T lymphocytes. It remains to be shown whether these infiltrates are responsible for the respective organ toxicities or represent merely an epiphenomenon of rIL‐2 treatment.

ISSN:0732-6580    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Summary:We examined the effect of levamisole (LMS) on the proliferative response and interleukin‐2 (IL‐2) concentration in OKT3‐, phytohemagglutinin‐, and concanavalin‐A‐stimulated lymphocyte cultures. Although proliferative response was enhanced in lymphocyte cultures. stimulated in the presence of LMS, similar levels of IL‐2 were observed in stimulated and unstimulated cultures. The mechanism of the enhancement effect of LMS on proliferative response was further characterized by studying its effects on the growth of IL‐2‐dependent CTLL‐2 cells in culture. Since this cell line has been shown to require 2‐mercaptoethanol (2‐ME) for normal growth in recombinant IL‐2, the effect of LMS on several parameters of its growth was compared with that of 2‐ME. Unlike 2‐ME, LMS did not enhance35S‐cystine uptake. Both compounds increased thiol concentration in the cell culture, but (oxidized) 2‐ME induced a greater increase. Generally, the effects of LMS on CTLL‐2 growth were quite similar to those of structurally unrelated compounds known to have antioxidant properties, and the demonstrated thiol requirement of this cell line for growth in recombinant IL‐2 was met by substituting LMS for 2‐ME. When the effect of LMS on IL‐2 receptor (IL‐2R) expression in CTLL‐2 cells was examined by a receptor‐ligand binding assay involving low levels (10‐80 pM) of125IL‐2, a modest increase in the level of IL‐2R expression was observed. The biologically active high‐affinity IL‐2R complex is believed to be preferentially bound at the low levels of125IL‐2 used here, suggesting a functional relevance for this effect of LMS. These observations should be useful in minimizing the cost and duration of in vitro expansion of lymphocytes for use in adoptive immunotherapy and should be applicable in improving the response of immunologically impaired patients to immunotherapy.

ISSN:0732-6580    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Summary:We have previously demonstrated that the successful transfer of rat chloroleukemia (Mia C51) cells to newborn rats is related to the host's inability to generate adequate levels of differentiation factor (DF). Thus, when the appropriate amount of DF was injected into rats bearing MIA C51 cells, the development of chloroleukemia was aborted. In the present study, we provide evidence that stimulation of endogenous differentiation activity (DA) production by the administration of a biologic response modifier (Imuvert) will likewise abort the development of chloroleukemia. Imuvert at 50 &mgr;g/ml had no direct effect on growth, viability, or differentiation of MIA C51 cells. However, when monocytes from young rats or adult rats were stimulated with Imuvert in vivo or in vitro, there was significant increase in DA production. Treatment of young rats with Imuvert aborted the development of chloroleukemia from transplanted MIA C51 cells. It is concluded that stimulation of endogenous DA production may provide a potentially useful approach in the treatment of leukemia.

ISSN:0732-6580    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Summary:The human Mx, an interferon (IFN)‐&agr;‐ and IFN‐&bgr;‐induced 76‐kd protein, is a homolog (Mx‐homolog) to the murine Mx protein, which is necessary and sufficient to provide adequate resistance against influenza virus in murine cells and in mice. Leukocytes from 36 patients with tumors (chronic myelogenic leukemia, hairy cell leukemia, and malignant melanoma) were monitored for their Mx‐homolog content before, during, and after rIFN‐&agr;‐2b therapy. Before therapy, only one patient was slightly positive for Mxhomolog. All 36 patients showed a significant increase of Mx‐homolog in their mononuclear cells within the first day of IFN therapy. During therapy, the Mx‐homolog levels remained elevated. After cessation of treatment, the Mx‐homolog content in the mononuclear cells decreased slowly; within 2 weeks, it was about 20‐30% of its value during therapy. However, even after 3 weeks, the Mx‐homolog was still detectable. The maximally induced Mx‐homolog concentration showed a significant correlation to the IFN dose given in vivo. These data indicate that the Mx‐homolog is an excellent marker for monitoring the activity of IFN during IFN therapy. In addition, the in vivo endogenous activation of the IFN system might be detectable by the determination of the Mx‐homolog despite the lack of circulating IFN.

ISSN:0732-6580    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Summary:The bolus injection of tumor necrosis factor (TNF)/cachectin into rats has been reported to induce shock and tissue injury similar to catabolic states seen in cachexia. In the present study, we administered TNF/cachectin to rats by either bolus injection or slow infusion and analyzed the influence on splenocyte mitogen‐induced proliferation and interleukin‐1 (IL‐1) production. Also, TNF administration was compared with lipopolysaccharide (LPS) injection and saline injection. Serum TNF levels were elevated by 30 min following the start of slow infusion, peaked at around 90 min, and remained elevated throughout the 3‐h sampling. However, analysis of serum TNF following a bolus injection showed that TNF peaked earlier (30 min) but then declined over the next 2.5 h. LPS infusion resulted in a serum TNF peak at 60‐90 min with a rapid decline to near baseline by the end of the 3‐h sampling. Spleens were removed from rats following either 3 h of infusion or 3 h following bolus injection, and single‐cell suspensions were prepared and analyzed in culture for lymphocyte proliferation to either concanavalin‐A (con‐A) or pokeweed mitogen (PWM). Adherent spleen cell cultures were also tested for IL‐1‐forming capacity in response to LPS. The slow infusion of TNF had a suppressive effect on splenic T lymphocyte responsiveness to con‐A. This suppressive effect was not observed in the response to the T cell‐dependent B cell mitogen PWM. In contrast to slow infusion, TNF bolus injection had no effect on T lymphocyte mitogen responsiveness. LPS‐inducible IL‐1 production was augmented by TNF infusion and bolus injection. LPS infusion and saline infusion had no demonstrable effect on LPS‐inducible IL‐1 production by splenocytes. Also, TNF, by infusion and/or bolus injection, was not alone sufficient to increase IL‐1 production by splenocytes. These data suggest that the administration of TNF/cachectin to rats alters the activity of immunocytes in addition to previously reported metabolic alterations. Furthermore, the results suggest that the method of TNF/cachectin administration (bolus versus slow infusion) can affect the extent of immune cell alteration.

ISSN:0732-6580    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Summary:A phase Ia‐Ib study was undertaken to treat melanoma patients with a constant dose of the anti‐GD3monoclonal antibody, R24, in combination with increasing dose levels of recombinant interferon‐&agr; (rHuIFN&agr;‐2a). Fifteen patients were treated on days 1‐5 and 8‐12 with a continuous 6‐h i.v. infusion of R24 (8 mg/m2) and escalating i.m. doses of rHuIFN&agr;‐2a. Peripheral blood lymphocytes were obtained at multiple times before and during treatment and monitored for changes in lymphocyte subpopulations and changes in natural killer and antibody‐dependent cellular toxicity functional activity. There were no consistent changes in most immune parameters; however, there was a decrease from pretreatment levels in the suppressor T cell (CD8+, CD11b+) subset and a dose‐dependent decrease in the helper/inducer (CD4+, Leu‐8+) T cell subset. The peak serum concentration of R24 was reached on day 5 of the study and was 9.4 &mgr;g/ml. During the second week of treatment, peak serum levels of R24 fell to <4 &mgr;g/ml. This finding was related to the development of human antimouse antibody, which would be detected as early as day 8 of the study. Binding of mouse Ig (R24) within the tumor bed was observed in 5 of 12 biopsy specimens. The maximal tolerated dose of the combination was doselevel IV, in which patients received 8 mg/m2of R24 and 50 × 106units of rHuIFN&agr;‐2a on days 1‐5 and 8‐12 of treatment.

ISSN:0732-6580    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Summary:A patient with an adenoid cystic carcinoma of the maxillary sinus was treated by adoptive immunotherapy involving intra‐arterial injection of lymphokine‐activated killer cells (a total number of 7 × 107cells) and recombinant interleukin‐2 (a total dose of 2.75 × 107units) in combination with radiotherapy (60Co; total irradiation dose of 5,000 rads). Consequently, it was found that bone formation was induced in the treated tumor, which was then replaced completely by lamellar bone tissue with myxomatous stroma. This finding indicates that the tumor cells composing certain adenoid cystic carcinoma can be converted into normal‐appearing, bone‐forming cells by current therapy and this differentiation phenomenon leads to cure of the tumor.

ISSN:0732-6580    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Summary:The efficacy of a low‐dose regimen of human recombinant interferon‐&ggr; was studied in 40 patients with metastatic or locally advanced renal cell carcinoma. Patients received 100 &mgr;g/m2/day as an infusion over 4 h. The intention was to find an active but tolerable regimen as a basis for future combination treatments with other cytokines or cytotoxic drugs. Activity of this low‐dose schedule had been reported. In the absence of rapid progression, treatment was given for at least 3 months, and in case of stable disease it was continued for prolonged periods in order not to miss late remissions. Toxicity was generally mild, with fever and constitutional symptoms predominating. Therapeutic efficacy was low with only one partial remission. Three patients had stable disease over 6, 9, and 15 months. This low‐dose schedule cannot be recommended for the treatment of renal cell cancer.

ISSN:0732-6580    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Summary:The effect of human urinary colony‐stimulating factor (CSF‐1) on the production of tumor necrosis factor (TNF) in vivo was assessed. Purified CSF‐1 was administered i.v. to rabbits 4 days prior to injection with lipopolysaccharide (LPS). TNF in the serum prepared from rabbits bled 90 min after LPS injection was measured using cytotoxicity assays employing mouse L929 cells and antirabbit TNF monclonal antibody. The results indicated that CSF‐1 was able to induce the production of TNF in vivo and had a synergistic effect withPropionibacterium acnes.

ISSN:0732-6580    

出版商:OVID    

年代:1990

数据来源: OVID