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At least 19 recordsLinked to original sources

Three schedules of recombinant human interleukin-2 in the treatment of malignancy: side effects and immunologic effects in relation to serum level.

Recombinant human interleukin-2 (rIL-2) was administered to 34 patients with advanced malignancy. Three schedules of rIL-2 administration employed were as follows: (A) 2-hr iv infusion of 6.7 X 10(5) U/m2/day (A1, 6 cases) or 2.2 X 10(6) U/m2/day (A2, 8 cases) for five consecutive days; (B) 24-hr continuous iv infusion of 3.3 X 10(5) U/m2/day (B1, 3 cases), 6.7 X 10(5) U/m2/day (B2, 7 cases) or 1.1 X 10(6) U/m2/day (B3, 5 cases) for 28 consecutive days; and (C) 24-hr continuous iv infusion of 6.7 X 10(5) U/m2/day (C, 5 cases) for 5 consecutive days per week for four weeks. The common side effects were fever (79%), eosinophilia (61%), malaise (56%), erythema or rash (50%), chills (38%) and nausea or vomiting (35%), with the dose-limiting toxicities being hypotension in group A, and renal dysfunction with fluid retention in groups B and C. In the case of 2-hr iv infusion, rIL-2 was rapidly cleared from the plasma, with a half life of about 30 min, while in the case of 24-hr continuous infusion, more than 1 U/ml serum IL-2 activity was maintained for 14 days in group B3. Natural killer (NK) and lymphokine-activated killer (LAK) activities were augmented by rIL-2 administration in patients of groups A, B3 and C. In eight patients of group B, NK and LAK activities transiently decreased after rIL-2 administration, and recovered by day 3. The percentage of IL-2 receptor and Leu HLA-DR positive cells reached the peak level on day 7 in group B. In patients of group C, the percentage of Leu HLA-DR positive cells as well as NK and LAK activities increased upon rIL-2 administration and decreased during an intermission of two days. However, the percentage of rIL-2 receptor positive cells increased during the intermission of rIL-2. The most effective schedule of rIL-2 administration was considered to be the schedule of group C on the basis of this study.

Adult

Possible immunological effects of psychotropic medication.

Psychoactive drugs provide an essential intervention in the care of organ transplant recipients, yet little is known of their effect on immunological function. Human and animal data on immunological effects of neuroleptic (e.g., haloperidol, phenothiazines) and antidepressant agents (e.g., tricyclic antidepressants, fluoxetine) lead to conflicting hypotheses. Lithium carbonate acts through the phosphoinositide system and has a bipolar effect on neuronal activity. Lithium is known to have immune-enhancing properties and is difficult to administer in the peritransplant period but nonetheless deserves study for possible beneficial effects on allograft function.

Humans

Some immunological effects of penicillamine.

Immunological effects of D- and D,L-penicillamine (PA) were studied in efforts to develop assays for synthetic D or D,L analogs and to contribute to the understanding of the mechanism(s) of action of D-PA in rheumatoid arthritis. At the highest doses tolerated by mice, D,L-PA did not significantly inhibit the development of haemagglutinating antibodies in vivo. In studies in vitro with T lymphocytes, D-PA at 1 mM concentration inhibited both concanavalin A- and phytohaemagglutinin-induced transformation as assayed by [3H]thymidine incorporation, but D-PA concentrations of 5 mM were required to inhibit concanavalin A-induced amino acid uptake. No effect of D-PA was observed either on the induction of cytotoxic T cells or on the attack of specifically sensitized T cells on target cells. It is of interest that D-PA at 1 mM concentration did inhibit lipopolysaccharide-induced transformation, which predominately stimulates B lymphocytes. The effects of PA on the induced transformation of T and B cells deserve further attention for studies with analogs of PA.

Animals

Alcohol-induced changes in the immune response: immunological effects of chronic ethanol intake are genetically regulated.

Experimental evidence on the immunomodulating effects of ethanol is contradictory and, in animals, the immunological effects of long-term alcohol intake may depend on the age of animal, amount of alcohol consumed, and nutritional composition of the administered diet. In this study, immunological effects of pair-feeding a 35% ethanol-containing Bio-Serv liquid diet for 6 weeks were evaluated using two major histocompatibility complex (MHC)-compatible inbred strains of rats (F344 and LEW). Food intake, rate of gain in body weight, and percentages of B cells, T cells, and T cell subtypes were not affected by ethanol intake. Also, proliferative responses of lymphocytes to T and B cell mitogens were similar in control and ethanol-fed groups of the two strains. Ethanol consumption had no significant influence on spleen weights and the antibody plaque-forming cell (PFC) response in F344 rats; however, in LEW rats, ethanol ingestion leads to a significant decrease (about 16%; p < 0.012) in spleen weight and a > 75% reduction in the PFC response. These results suggest that a non-MHC-encoded gene(s) regulates the ethanol-mediated immunosuppression of the PFC response. Thus, LEW-F344 combination may provide an excellent model to characterize genetic factors which determine sensitivity/resistance to immunological effects of ethanol ingestion.

Alcohol Drinking

[Comparative immunologic effectiveness of variants of the DTP vaccine].

The immunological effectiveness of two batches of adsorbed DPT vaccine, the batch with the normal content of antigens (control) and the batch with the content of diphtheria and tetanus toxoids reduced to 20 Lf/ml and 5 BU/ml respectively (test batch), has been studied under the conditions of controlled trial. As a result, the reduction of the antigenic content of adsorbed DPT vaccine has been found to exert no negative influence on the immunological effectiveness of the diphtheria, tetanus, and pertussis components of this preparation under the conditions of the new immunization schedule.

Antibodies, Bacterial

Comparison of the time course of morphine's analgesic and immunologic effects.

UNLABELLED: Morphine, an opioid analgesic commonly prescribed and abused, produces immune-altering effects. Whether morphine's antinociceptive and immunologic effects occur concurrently is unknown. Therefore, we investigated the time course of morphine's immunologic and antinociceptive effects. Rats were given a 15-mg/kg morphine injection (subcutaneously), and experimental assessments were taken at 30 min, 1 h, 2 h, 6 h, 12 h, and 24 h after treatment. Immune measures included natural killer (NK) cell activity, proliferation of splenic T and B lymphocytes, and cytokine production. Antinociception was assessed by using the tail withdrawal assay. Results show that morphine's immunomodulatory effects on NK cell activity begin within 30 min, continue for at least 12 h, and return to control values by 24 h. In contrast, proliferation of splenic T and B cells and interferon-gamma production are not altered within 30 min; maximal suppression occurs at 1 h, and recovery begins within 2 h. In all immune measures, therefore, maximal suppression is present at the 1-h time point, and recovery is complete within 24 h. Morphine induces antinociception 30 min to 2 h after drug administration; recovery is complete within 6 h. These results suggest the possibility that different mechanisms modulate morphine's immunologic and analgesic effects. IMPLICATIONS: Acute morphine treatment in rats produces immune alterations and antinociception. Although there are slight differences in morphine's maximal immunological and antinociceptive effects, morphine suppresses immune status at time points concordant with its antinociceptive effects. These effects should be considered when administering morphine to patients whose systems are immunocompromised.

Analgesia

Addition of dacarbazine or cisplatin to interferon-alpha/interleukin-2 in metastatic melanoma: toxicity and immunological effects.

The combination of chemotherapy and immunotherapy seems to improve response rate in metastatic melanoma. We investigated the effects on toxicity and immunological effects of a single dose of dacarbacin (DTIC; 850 mg/m2) or cisplatin (CDDP; 100 mg/m2) added to subsequent immunotherapy with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). Twelve patients, who did not respond to IFN-alpha/IL-2 alone were studied. Six received DTIC and IFN-alpha/IL-2, and six received CDDP and IFN-alpha/IL-2. DTIC did not add significant toxicity except for nausea. Significant thrombocytopenia was observed in two patients after CDDP. Although CDDP led to grade 3 nephrotoxicity in two patients, the IL-2-induced fluid retention was less severe than with IFN-alpha/IL-2 alone. Pharmacokinetics of IL-2 were not altered by DTIC, but higher IL-2 serum levels were found in patients with grade 3 nephrotoxicity after CDDP. The IL-2-related induction of secondary mediators (interferon-gamma, tumour necrosis factor-alpha, soluble CD25) was not impaired by chemotherapy and the induction of neopterin was significantly higher after addition of CDDP. One partial response was observed after addition of DTIC to IFN-alpha/IL-2, and one after addition of CDDP. The addition of a single dose of DTIC or CDDP to IFN-alpha/IL-2 is fairly well tolerated and does not abolish induction of secondary mediators. Randomized trials are necessary to test the clinical efficacy.

Adjuvants, Immunologic

[Immunological effect of recombinant interferon-gamma in renal cell carcinoma].

The immunological effect of interferon-gamma (IFN-gamma) was investigated in 18 cases of renal cell carcinoma before and after the operation. In 6 patients, IFN-gamma was administered preoperatively for 21 days (administration group), while 12 patients underwent nephrectomy alone without preoperative treatment (control group). The peripheral immunological effects were measured at before and 12 days after the operation in the administration group and at 11 days in the control group. In the administration group, a marked increase was noted in the test of antibody dependent cell-mediated cytotoxicity (ADCC) activity and natural killer (NK) activity, and slight increase in CD4/8 and CD11b. In low stage cases, no appreciable effect was obtained by the administration of IFN-gamma. However, in high stage cases, IFN-gamma tended to increase the value of ADCC activity and NK activity. Immunohistochemical studies of tumor infiltrating lymphocytes in renal cell carcinoma showed a high incidence of CD8 and CD11b in the administration group. Moreover, the presence of CD8 was higher than that of CD4 in the administration group in contrast to the results of the peripheral blood analysis.

Carcinoma, Renal Cell

Topical flunisolide treatment of perennial rhinitis: clinical and immunological effects.

We studied the clinical and immunological effects of three months' treatment with intranasal flunisolide (100 micrograms daily) in 18 allergic patients with perennial rhinitis. 17 were hypersensitive to house dust mite and one to Parietaria pollen only. We found no significant changes in white blood cell count, serum levels of IgE and nasal IgA. However the treatment induced a marked improvement of clinical symptoms in all cases, and we observed a significant reduction of total IgE in nasal secretion. Flunisolide seems to exert this effect through its antiinflammatory action on the nasal mucosa.

Administration, Intranasal

Topical flunisolide treatment of perennial rhinitis: clinical and immunological effects.

We studied the clinical and immunological effects of three months' treatment with intranasal flunisolide (100 micrograms daily) in 18 allergic patients with perennial rhinitis. 17 were hypersensitive to house dust mite and one to Parietaria pollen only. We found no significant changes in white blood cell count, serum levels of IgE and nasal IgA. However the treatment induced a marked improvement of clinical symptoms in all cases, and we observed a significant reduction of total IgE in nasal secretion. Flunisolide seems to exert this effect through its antiinflammatory action on the nasal mucosa.

Administration, Intranasal

Clinical, pharmacologic, and immunologic effects of 2'-deoxycoformycin.

Clinical, pharmacologic, and immunologic effects of 2'-deoxycoformycin (dCF) were evaluated in 15 patients with advanced malignancies. Toxicity was less severe with a low dose (4 mg/m2) of dCF, but this dose still resulted in suppression of cellular adenosine deaminase activity, skin test reactivity, and lymphocyte responses to mitogens. Improvement in cutaneous T cell lymphoma plaques was seen after dCF. Further investigations of antitumor efficacy with the use of this low dosage schedule should continue in patients with hematologic neoplasms, and additional preliminary studies of the combination of an adenosine deaminase inhibitor with an adenosine analog should also be considered.

Adenosine Deaminase

Use of cryopreserved lymphocytes for assessment of the immunological effects of interferon therapy in renal cell carcinoma patients.

Experiments were designed to assess whether cryopreserved PBL could be used to monitor the immunological effects of IFN-alpha therapy in renal cell carcinoma (RCC) patients. It was found that programmed freezing and thawing of peripheral blood lymphocytes (PBL) from normal blood donors did not substantially change lymphocyte subset proportions and that cryopreserved PBL were able to proliferate in response to IL-2. It was also possible to activate the cytolytic activity of frozen PBL, and the frozen leukocytes did not lose their ability to secrete IFN-gamma after PHA activation. We have used these findings to investigate the immunological effects of IFN-alpha therapy in RCC patients. Cryopreservation of PBL samples collected from various patients over a period of 9-14 months enabled us to compare the in vitro reactivity of PBL from individual RCC patients repeatedly and under standard conditions. It was found that IL-2 induced proliferative responses of PBL from IFN-alpha non-responders, collected prior to IFN-alpha therapy, were significantly decreased as compared to those from normal blood donors. The proliferative responses of PBL from IFN-alpha responders, collected prior to IFN-alpha therapy, did not substantially differ from normal controls. Culture of PBL from IFN-alpha responders for 3 days in IFN-alpha-containing medium increased their lytic activity towards RCC targets, whereas no such increase was observed with non-RCC targets or using PBL from IFN-alpha non-responders or PBL from normal-blood donors. Enzyme-linked immunospot (ELISPOT) assays performed with cryopreserved lymphocytes from IFN-alpha non-responding RCC patients, collected prior to IFN-alpha therapy, revealed a substantially decreased ability to secrete IFN-gamma, as compared to IFN-gamma secretion of PBL from IFN-alpha responders or normal blood donors.

Carcinoma, Renal Cell

Immunological effects of arsenic compounds on mouse spleen cells in vitro.

Immunological effects of arsenic compounds on mouse spleen cells in vitro were examined. Three kinds of arsenic compounds: sodium arsenite, sodium arsenate and dimethyl arsenic acid, at high doses, suppressed the plaque-forming cell response to sheep erythrocytes and the proliferative response to mitogens, whereas at low doses they enhanced both responses. And each of arsenic compounds differs in strengths at which the modulation effects on both responses were exerted. The strength was comparable to general toxicity of arsenic compounds.

Animals

[Immunological effects of corticosteroids in man (author's transl)].

Corticosteroids are efficient in many kidney diseases but their use is commonly empirical. Their anti-inflammatory effects are often difficult to dissociate from their immunological effects. These consist in inhibiting lymphocyte proliferation without greatly affecting their cytotoxicity and antibody synthesis. Corticosteroids induce lymphopenia and influence the distribution of lymphocytes subpopulations. This leads to prevention of cells homing in target organ and markedly affects immunoregulation. This latter action may explain the beneficial effects of corticosteroids in diseases with profound disturbances in immunity.

Adrenal Cortex Hormones

[Immunological effectiveness of a dried group-A meningococcal polysaccharide vaccine].

The immunological effectiveness of dried group A meningococcal polysaccharide vaccine, developed at the Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow, for children aged 5-14 years was studied. The intensiveness of the immune response of children to 0.5 ml of the vaccine introduced in a single injection was evaluated by a rise in the level of agglutinating antibodies to group A meningococcal polysaccharide in the sera of the vaccinees 3-4 weeks after immunization with the following optimum doses: 25 micrograms for children aged 5-8 years, 50 micrograms for children aged 9-13 years and 75 micrograms for children aged 14 years and over. The vaccine was shown to be highly immunogenic. Antibodies to group A meningococcal polysaccharide were identified as IgM. These antibodies in a titer of 1:40 and higher could be detected in 90% of the vaccinated children in the younger age group, 7 months after immunization.

Adolescent

Sequential biochemotherapy for metastatic colorectal cancer using fluorouracil, folinic acid, thymopentin and interleukin-2: clinical and immunological effects.

BACKGROUND: A phase II study was performed to evaluate the clinical and immunological effects of a regimen of fluorouracil (5-FU) and folinic acid (FA) combined with thymopentin (TP-5) and interleukin-2 (IL-2) in the treatment of patients with metastatic colorectal cancer. PATIENTS AND METHODS: Forty-five evaluable patients with measurable colorectal cancer and no prior therapy for metastatic disease were treated with 5-FU 400 mg/m2/d and FA 200 mg/m2/d i.v. on days 1-5, TP-5 50 mg s.c. on days 8-11, and IL-2 9 MU/m2 s.c. twice daily on days 12-16. Cycles were repeated at 4-week intervals if toxicity had resolved. Immunological changes were evaluated in 13 patients and compared with a well matched series of 13 patients treated with the same regimen without TP-5. RESULTS: Two complete responses and 17 partial responses were seen (42%; 95% confidence interval, 28% to 56%). Fifteen patients (33%) had stable disease. The median time to progression was 8.5 months and the median survival 13 months. Treatment was reasonably well tolerated, and there was no overlapping toxicity or interference between chemotherapy and biotherapy. Hematological and immunological changes during treatment were qualitatively similar to those expected with IL-2 +/- chemotherapy. Quantitatively, significant changes (higher levels of IL-2, CD25 and IFN-gamma, and lower levels of sIL-2R) were observed in patients given TP-5. CONCLUSION: The combination of 5-FU + FA and TP-5 + IL-2 is effective in advanced colorectal cancer with acceptable toxicity. Immunological data suggest that TP-5 may modulate the action of IL-2 in the clinical setting. However, improved treatment approaches are needed, and the interactions between thymic hormones and cytokines should be further explored.

Adult

Antitumor and immunologic effects of a pyridine-extracted fraction of Propionibacterium acnes.

The antitumor and immunological effects of a pyridine extractable fraction of Propionibacterium acnes were tested in a murine ovarian teratocarcinoma (MOT) model. Previous studies have demonstrated that tumor rejection in this model depends upon sequential activation of tumoricidal neutrophils (PMNs) followed by cytostatic macrophages. The pyridine extract significantly prolonged the survival of mice challenged with 10(3) or 10(4) MOT cells but had little impact on a 10(5) tumor inoculum. In vivo cytoreduction occurred within the first 24 h following IP treatment which correlated temporally with the influx of tumoricidal PMNs into the peritoneal cavity. Immunotherapy failure in mice challenged with 10(5) MOT cells occurred between 48 and 72 h after treatment when macrophage chemotaxis into the peritoneal cavity was initiated. Although injection of unfractionated bacteria activated MOT-cytostatic macrophages, the pyridine extract was deficient in this regard. Intraperitoneal injection of the pyridine extract resulted in an early (day +1) depression and late (day +5) enhancement of peritoneal NK cytotoxicity. These data suggest that the retention of neutrophil-activating moieties in the pyridine extract are sufficient for antitumor effects against low tumor inocula while the depletion of macrophage-activating determinants results in diminished effects against larger tumor cell challenges.

Adjuvants, Immunologic