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Biomedical subjects

H Kirchner

Publications and source records attributed to H Kirchner.

At least 145 records · Page 8Linked to original sources
PubMed1996

Induction of a cytokine network by superantigens with parallel TH1 and TH2 stimulation.

Superantigens cross-link the MHC class II molecule on accessory cells with the V beta region of the TCR outside the antigen binding sites. In this study, we compared the capacity of the staphylococcal entertoxins (SE) A, B, C1, C2, C3, D, and E, the toxic shock syndrome toxin (TSST) 1, the exfoliative toxin (ExFT) A, and the Streptococcus pyogenes erythrogenic exotoxins (SPE) B and C to induce cytokine release in human peripheral blood mononuclear cells. We showed that all toxins tested induced IL-1 alpha and beta, IL-2, IL-4, IL-6, IFN-gamma, and TNF-alpha, but not IFN-alpha. However, we found that SPEB differed from all other toxins tested, because its cytokine induction was significantly lower than that of the other toxins. This was not true of IL-6 and IL-10 induction, in which SPEB showed similar amounts of IL-6 compared with all other toxins and of IL-10 in comparison to SEC2. SPEB showed a specificity for TH2 cells, whereas the other toxins stimulated TH1 as well as TH2 cells very strongly. As a result, superantigens appear to be able to uncouple the TH1/TH2 antagonism. Collectively, our results indicate that SPEB seems not to be a superantigen or represents a different group of microbial superantigens. Furthermore, superantigens stimulate TH1 as well as TH2 cells without any preference and therefore they are able to induce humoral as well as cellular immunity. This could be one reason for the existence of autoantibodies and autoreactive T cells in autoimmune diseases and one major step in the beginning of the induction of autoreactivity.

Antibody Formation↗
PubMed1996

Induction of a proinflammatory cytokine network by Mycoplasma arthritidis-derived superantigen (MAS).

Mycoplasma arthritidis is an arthritogenic organism for rodents, producing a superantigen (MAS). It has been postulated that mycoplasmas or superantigens thereof might play a role in human rheumatoid arthritis. Since M. arthritidis fulfills both, the present study was performed to investigate MAS-specific cytokine induction. Human or murine leukocytes were stimulated with MAS, staphylococcal enterotoxin E (SEE), or lipopolysaccharide (LPS). Cytokines were measured by ELISA, Bioassay, and RT-PCR. The response to MAS in humans was individually restricted, in contrast to the response to SEE or LPS. Furthermore, MAS showed the same capacity for inducing proinflammatory cytokines as interleukin (IL)-1 IL-6, and IL-8 as SEE and LPS. However, MAS showed a significantly decreased capacity to induce the anti-inflammatory cytokine IL-10 and IL-1RA. In mice, the reactivity to MAS was strictly MHC-II restricted, in contrast to that of SEE or LPS. The individual response to MAS in humans might be explained by the difference of the HLA-DR haplotype because H-2-differing mouse strains showed the same discrepancies. MAS induced an overproduction of proinflammatory cytokines, when its ability to induce proinflammatory and anti-inflammatory cytokines was compared with those of SEE and LPS. The individual response may explain an MHC linkage, and the failure to induce anti-inflammatory cytokines may be the reason for a chronic disease in contrast to acute inflammation.

Animals↗
PubMed1996

Immunologic properties of Epstein-Barr virus-seronegative adults.

Epstein-Barr virus (EBV) seronegativity is rare in people > 20 years old. However, some persons remain EBV-seronegative for nearly their whole lives. The aim of this study was to examine properties of the immune system of EBV-seronegative adults that could contribute to long-term EBV seronegativity. Therefore, differential blood cell counts and lymphocyte subpopulations were determined, and the production of interferon (INF)-alpha and -gamma and interleukin (IL)-6 and -2 in a whole blood assay was investigated. Whereas no differences in the distribution of lymphocyte subpopulations between EBV-seronegative and -positive adults were found, a significant higher percentage of monocytes in EBV-seronegative adults was observed. Significantly more IFN-alpha and IL-6 were detected in culture supernatants of EBV-seronegative persons after stimulation with Newcastle disease virus. In contrast, no differences in the induction of the lymphokines IFN-gamma and IL-2 were seen. These data suggest that faster and higher production of IFN-alpha and IL-6 amy protect EBV-seronegative adults against EBV infection.

Adult↗
PubMed1996

Major depressive disorder is associated with elevated monocyte counts.

One of the most consistently reported findings in depression has been leucocytosis. In 33 in-patients with major depressive disorder, we assessed white blood cell count (WBC) and lymphocyte subsets four times over a period of 6 weeks. The control group consisted of 44 healthy subjects. Shortly after admission, we detected significant increases in the numbers of leucocytes, granulocytes, platelets and monocytes in the depressed patients. Patients who recovered well during hospitalization showed a decrease in monocyte counts, whereas those with slower clinical improvement had significantly higher monocyte counts than the control group. This longitudinal study demonstrates that monocytes may play a role in the acute phase of depression and could provide an explanation for immunological dysfunction in depressive states.

Adolescent↗
PubMed1996

Cytogenetic studies in renal cell carcinoma patients receiving low-dose recombinant interleukin-2-based immunotherapy.

A variety of cytogenetic aberrations have been reported in sporadic and familial renal cell carcinoma. Rearrangements of the short arm of chromosome 3 (3p), trisomy 17, and nuclear hyperdiploidy have been reported to be common clonal chromosome changes. We analyzed a total of ten tumor-derived cell lines from patients who underwent nephrectomy for renal cell carcinoma employing conventional cytogenetics. All patients received an immunomodulatory therapy based on recombinant interleukin-2 (rIL-2). Tumor stage and grade, histo- and cytopathology, and patients' response to immunotherapy were assessed and correlated statistically to rearrangement of 3p, trisomy 17, and nuclear hyperdiploidy. Trisomy 17 as clonal aberration could be revealed only in papillary renal cell carcinoma, whereas tumors with compact or tubulopapillary growth pattern lacked this abnormality (p < 0.002). One of 3 patients with diploid or near-diploid karyotype (< or = 49 chromosomes) achieved a partial remission while two presented with stable disease after immunotherapy. In contrast, all 6 patients with tumor progression upon rIL-2-based immunotherapy revealed hyperdiploid (> 49 chromosomes) karyotypes. The correlation between hyperdiploidy and tumor progression was found to be statistically significant (p < 0.029). Interestingly, the only patient achieving an objective tumor remission after immunotherapy presented with a normal diploid karyotype. Our findings suggest tumor hyperdiploidy as an adverse prognostic factor in renal cell carcinoma patients receiving rIL-2-based immunotherapy.

Aged↗
PubMed1996

Recent progress in the tumor necrosis factor-alpha field.

Tumor necrosis factor (TNF is used synonymously with TNF-alpha) is a pleiotropic cytokine. The effects of TNF were first described in the last century, but the soluble factor was discovered in 1975. Now TNF is one of the most important cytokines investigated by scientists from different fields. This short review briefly summarizes the state of the art and adds the news of the last 2 years. The progress in the field of TNF is focussed on gene organization and transcription, gene polymorphism, biochemistry of TNF, TNF receptors and the biological role of TNF in autoimmune diseases, infectious diseases, transplantation, cancer and TNF functions on endothelial cells.

Animals↗
PubMed1996

Interleukin-2 based home therapy of metastatic renal cell carcinoma: risks and benefits in 215 consecutive single institution patients.

PURPOSE: In 215 consecutive patients with advanced metastatic renal cell carcinoma seen at a single institution the efficacy and tolerance of different subcutaneous recombinant interleukin-2 based home therapies were assessed. MATERIALS AND METHODS: Treatment consisted of subcutaneous recombinant interleukin-2 alone and subcutaneous recombinant interleukin-2 in combination with recombinant interferon-alpha 2 with or without intravenous 5-fluorouracil. RESULTS: Overall objective response rate in 215 patients was 33% (95% confidence interval 26 to 39%). Among 16 patients receiving recombinant interleukin-2 alone there was 1 partial remission (overall response 6%). In 79 patients receiving recombinant interleukin-2 and interferon-alpha 2 in combination 6 complete and 16 partial remissions occurred (overall response 28%). Of 120 patients receiving a combination of recombinant interleukin-2, recombinant interferon-alpha 2 and 5-fluorouracil 13 achieved a complete and 34 a partial remission (overall response 39%). Of all patients 5% achieved long-lasting remissions and remain disease-free. Multivariate analyses identified pretreatment erythrocyte sedimentation rate greater than 70 mm. per hour and lactic dehydrogenase greater than 280 units per l. as independent prognostic factors of major significance (p < or = 0.0001) in metastatic renal cell carcinoma. Additionally, neutrophil count greater than 6,000/microliters., hemoglobin less than 100 gm./l., extrapulmonary metastases and bone lesions were identified as minor (p < or = 0.006) prognostic variables. Patients were assigned to 1 of 3 risk categories according to cumulative risk score defined as the function of the sum of all 6 independent variables. In 116 intermediate risk patients 2-year survival was 65% (median survival not reached after 32 months) with recombinant interleukin-2, recombinant interferon-alpha 2 and 5-fluorouracil, as opposed to 27% 2-year survival (median survival 15 months) with recombinant interleukin-2 and interferon-alpha 2 (p < 0.0001), and 0% (median survival 4.8 months) with single agent recombinant interleukin-2. In the majority of patients systemic toxicity of subcutaneous recombinant interleukin-2 based protocols was limited to grade 1 or 2 constitutional symptoms, that is fever, chills, malaise and anorexia, which allowed for outpatient therapy. CONCLUSIONS: The present outpatient recombinant interleukin-2 triple drug combination protocol was as effective as the most aggressive intravenous recombinant interleukin-2 regimen available. Combination home therapy eliminated the need for inpatient and/or intensive care as required for intravenous cytokine administration and, thereby, it substantially improved the therapeutic index and cost-effectiveness of recombinant interleukin-2 therapy in metastatic renal cell carcinoma stratified for risk.

Antineoplastic Agents↗
PubMed1996

[Prevalence of hepatitis C virus in blood donors and comparison of 4 different anti-HCV differentiation tests].

In 1994 we tested 30,208 blood donations in Lübeck with the Abbott HCV EIA 2.0. 88 specimens of 47 blood donors who were repeatedly reactive were the basis of comparative investigations with the Chiron RIBA HCV 2.0 and 3.0, the Abbott Matrix HCV, the Wellcozyme HCV Western Blot (Murex) and the PCR (Amplicor HCV Test, Roche Diagnostic Systems). Our results suggest that the minimal prevalence of HCV RNA amounts to approximately 0.13%, the incidence per year to 0.013%. The minimal prevalence of anti-HCV amounts to 0.27%. Anti-core antibodies are the most frequent anti-HCV antibodies. They may be the only detectable antibodies during the early phase of the infection. The Chiron RIBA HCV 3.0 with the synthetic peptide c22p is not sufficiently sensitive for anti-core antibodies and may therefore fail to recognize viremic specimens.

Blood Donors↗
PubMed1996

[Blood leukocytes are not a primary latent site of cytomegalovirus].

Conflicting results do exist regarding blood leukocytes as a site of CMV latency. In an attempt to detect latently infected blood cells we studied CMV major immediate early (MIE) antigen expression in monocytes or mononuclear leukocytes from 80 blood donors (71 seropositive) after in vitro stimulation and subsequent antigen detection by immunocytochemistry (detection limit 1 positive cell/10(6) cells). None of the more than 800 cytospin preparations investigated turned out to be positive. Additionally the granulocyte macrophage colony stimulating factor (GM-CSF)/hydrocortisone (HC) stimulated monocytes were analysed by reverse transcriptase PCR for the presence of MIE mRNA and were also completely negative. In contrast to the negative findings in blood samples, we detected CMV DNA by PCR in 6 out of 20 suddenly deceased individuals in tissue samples of the lung, but not in those of other organs. We conclude that we have no evidence that blood leukocytes are a site of latent CMV. The transmission of CMV by blood transfusions may be mediated by rare phagocytes that transiently bear CMV after uptake from infected endothelial cells.

Blood Donors↗
PubMed1996

[Blood donation after reaching 65 years of age].

European regulations for blood donation recommend a maximum donor age of 65 years. On the other hand, the percentage of the population in this age group is rapidly increasing in Western countries, and in autologous blood donation programs this limitation has already been abandoned. In a prospective study we examined blood donation in elderly donors (18 male and 5 female; mean age 65 years, range 64-69) in comparison to a younger control group (15/9; 58, 55-63). All donors were regular blood donors and had donated for at least 3 years. We investigated the exercise capacity before and after donation of 450 ml whole blood by examination of the physical working capacity (PWC) at heart rates of 110/min and 130/min through treadmill exercise testing and determined the blood viscosity. Additionally, whole-blood count, hemoglobin, plasma-ferritin levels and total iron binding capacity were measured immediately after donation and on days 7, 28 and 49. We found a decrease in whole-blood viscosity and a moderate increase in PWC at heart rates of 110/min and 130/min after donation in both groups. Red cell count and values of hemoglobin and ferritin were significantly lower in both groups after donation and returned to pre-donation values by day 49 in the younger control group. We detected no deterioration in exercise capacity after whole-blood donation in elderly blood donors over 65 years when compared with a younger control group. We suggest that blood donation in otherwise healthy persons aged over 65 years should be accepted.

Aged↗
PubMed1995

Coincidence of Epstein-Barr virus reactivation, cytomegalovirus infection, and rejection episodes in renal transplant recipients.

Reactivation of the Epstein-Barr virus was reported to occur frequently under immunosuppressive therapy following organ transplantation. However, little is known about the clinical significance of these EBV reactivations. Therefore, we searched for correlations among the treatment with various immunosuppressive drugs, the incidence of CMV infections, rejection crises, and serological signs of EBV reactivation. EBV-specific antibodies were measured with novel ELISAs, utilizing the recombinant antigens p72 (for anti-EBV nuclear antigen [EBNA]1-IgG), p54, and p138 (anti-early antigen [EA]-IgM, -IgG, -IgA) in a follow-up study of 79 renal transplant recipients. Patients receiving antithymocyte globulin or antilymphocyte globulin therapy showed increasing anti-EA-IgG and -IgA more often than did patients not receiving antithymocyte globulin or antilymphocyte globulin therapy (P < 0.05). In patients receiving OKT3 antirejection therapy, anti-EA-IgM seroconversion was found more frequently (P < 0.01). A significant correlation was also found between groups of patients who had had at least one rejection episode versus patients without any sign of organ rejection, and the incidence of increasing anti-EA-IgG (P < 0.05). Since in most of these patients signs of EBV reactivation followed the appearance of the rejection episode, this may not be due to viral-induced rejection but may be caused by the reinforced immunosuppression during antirejection therapy. As opposed to patients with no signs of CMV infection and with nonsymptomatic CMV infection, patients undergoing symptomatic CMV infection showed anti-EA-IgM seroconversion (P < 0.01), increasing anti-EA-IgA (P < 0.01), and decreasing anti-EBNA-IgG (P < 0.01) more frequently. Our results confirm the role of immunosuppressive therapy in the pathogenesis of EBV reactivation. We further demonstrate a striking coincidence of EBV reactivation and symptomatic CMV infection.

Antibodies, Viral↗
PubMed1995

Influence of serum on zinc, toxic shock syndrome toxin-1, and lipopolysaccharide-induced production of IFN-gamma and IL-1 beta by human mononuclear cells.

Measurement of cytokine secretion in vitro is usually performed in culture medium supplemented with human serum. We compared the secretion of interferon-gamma and interleukin-1 beta as a parameter for lymphocyte and monocyte activation in RPMI 1640 medium supplemented with fetal calf or autologous serum in serum-free medium and protein-free medium. Four different stimulatory mechanisms were tested: phytohemagglutinin, toxic shock syndrome toxin-1 (TSST-1), lipopolysaccharide (LPS), and zinc ions. We found that the optimal stimulatory zinc concentration depended on the total protein content of the medium, whereas the monokine levels were dependent on the concentration of transport proteins such as transferrin. Monokine induction by LPS or TSST-1 were each influenced by the protein and serum composition in a specific manner. Our results show that the differing mechanisms of cytokine induction are influenced by the medium and serum composition in a diverse but specific manner. Serum- or protein-free medium are especially suitable after superantigen challenge when LPS activity needs to be ruled out or after activation by agents with only a weak stimulatory capacity.

Bacterial Toxins↗
PubMed1995

Biochemotherapy of advanced metastatic renal-cell carcinoma: results of the combination of interleukin-2, alpha-interferon, 5-fluorouracil, vinblastine, and 13-cis-retinoic acid.

We conducted a phase I/II clinical trial evaluating the sequential outpatient combination of S.C. recombinant human interleukin-2 (rIL-2; given at 10 MIU/m2 b.i.d. on days 3-5 weeks 1 and 4 and at 5 MIU/m2 on days 1, 3, and 5 of weeks 2 and 3), s.c. recombinant human alpha-interferon (rIFN-alpha; given at 6 MIU/m2 on day 1 of weeks 1 and 4 and on days 1, 3, and 5 of weeks 2 and 3 and at 9 MIU/m2 on days 1, 3, and 5 of weeks 5-8), i.v. bolus 5-fluorouracil (5-FU; given at 1,000 mg/m2 once weekly during weeks 5-8), and i.v. bolus vinblastine (given at 6 mg/m2 once weekly during weeks 5 and 8) in conjunction with p.o. 13-cis-retinoic acid (13-C-RA; given at 35 mg/m2 daily during weeks 1-8). Therapy was always given in the outpatient setting. Grade 3 constitutional symptoms (malaise, chills, fevers, anorexia) were observed in 4%-8% of treatment cycles and required a 50% reduction in the doses of rIL-2 and rIFN-alpha. None of the patients experienced major 5-FU-related toxicities such as severe diarrhea and/or stomatitis; up to 20% of patients developed vinblastine-associated peripheral polyneuropathy, which was reversible after the cessation of therapy. 13-cis-Retinoic acid produced no significant side effect; no toxic death occurred. Among 24 patients with progressive metastatic disease, there were 4 complete remissions (lung, lymph nodes) and 6 partial remissions (lung, pleura, liver, lymph nodes, and peritoneal carcinosis), for an overall objective response rate of 42% (95% confidence interval, 22%-63%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1995

Low prevalence of diphtheria antitoxin in children and adults in northern Germany.

Recent outbreaks of diphtheria in neighbouring eastern European countries and in the Russian Federation prompted us to evaluate immunity to diphtheria in a sample of 400 healthy individuals (210 male, 190 female) from northern Germany. An age-stratified study population was chosen, including newborns, children, adults and elderly persons over 60 years divided into 8 subgroups of 50 persons each. Diphtheria antitoxin was tested by enzyme immunoassay. The median antitoxin titre was 0.39 IU/ml. There was no difference in the median antitoxin titres of men and women. Inadequate immunity to diphtheria was detected in more than 90% of the 400 individuals tested, including 4% who completely lacked immunity (titre < 0.01 IU/ml), a further 20% with minimal protection (titre 0.01-0.1 IU/ml) and the majority of 69% who showed relative protection for less than one year (titre 0.1-1.0 IU/ml). Only 7% exhibited lasting protection for more than five years (titre > 1.1). Newborns and persons over 50 years of age constituted the least protected groups, with significantly lower median antitoxoid titres than the other age groups (p < 0.001). The absence of protective immunity in 7 of the 50 newborns examined (14%) reflects the inadequate protection of women of reproductive age. Children aged 1 to 10 years were the best immunized and protected group. The results suggest that routine booster immunizations of the majority of the adult population would be advisable in view of the ongoing migration from and the visits to high-risk areas.

Adolescent↗
PubMed1995

Defective production of interleukin-2 in patients with idiopathic Parkinson's disease.

The pathogenesis of Parkinson's disease (PD) is largely unknown. Recently, several studies have presented evidence of an immunological dysfunction in patients suffering from PD. We studied the immune responsiveness of patients with idiopathic PD (n = 20) by investigation of the ability of peripheral blood mononuclear cells to produce cytokines after mitogenic stimulation in a whole blood assay. A group of age-related healthy blood donors served as control (n = 19). Additionally, white blood count, leukocyte differentiation and lymphocyte subtyping were performed. PD patients had a significantly higher neutrophil count, but analysis of T-cell subsets showed no difference between the two groups. In peripheral blood, secretion of interleukin-2 (IL-2) after mitogenic stimulation was significantly diminished in the patients' group (p < 0.01), whereas values of IFN-alpha 2, IL-6, IFN-gamma and sIL-2R were comparable in both groups. IL-2 production correlated negatively with the mean annual dose of levodopa treatment and correlated significantly (p < 0.002) with amantadine uptake. Analysis of sex, age, duration of illness and other drug intake revealed no correlation with cytokine release. Our findings support the view that there is a selective abnormality in the immune repertoire of peripheral blood lymphocytes in patients suffering from PD, the reasons for which need to be explored.

Aged↗
PubMed1995

Production of interferons and lymphokines in leukocyte cultures of patients with schizophrenia.

Recently, several lines of evidence have suggested the possible of immunological dysfunction in the pathogenesis of schizophrenia. We therefore investigated the ability to produce interferons and lymphokines in response to mitogenic or viral stimulation in a whole blood assay of 37 schizophrenic patients (DSM-III-R) and of 42 healthy blood donors. Phytohaemagglutinin (PHA) was used for the induction of interleukin-2 (IL-2), interferon gamma (INF gamma), interleukin-6 (IL-6) and the soluble interleukin-2 receptor (sIL-2R) and Newcastle Disease Virus (NDV) for the induction of interferon alpha 2 (INF alpha 2). All lymphokines and, in addition, the sIL-2R in the sera were determined by ELISA technique. The psychopathological status of the patients was assessed by psychiatrists according to internationally accepted standards. The patient group showed a trend to lower levels of the interferons alpha 2 and gamma and a significant decrease of IL-2 production. The sIL-2R levels were significantly increased in the sera of schizophrenic patients. The latter increase was associated with a poor assessment of prognosis (Strauss and Carpenter). This association appears to be of interest. However, its significance is not understood, since longitudinal studies could not be performed.

Adult↗
PubMed1995

Chemoimmunotherapy of advanced malignant melanoma: sequential administration of subcutaneous interleukin-2 and interferon-alpha after intravenous dacarbazine and carboplatin or intravenous dacarbazine, cisplatin, carmustine and tamoxifen.

Both chemotherapy and interleukin-2 and/or interferon-alpha produce objective responses in a proportion of advanced malignant melanoma patients. While duration of response to chemotherapy is short, i.e. usually below 4 months, immunotherapy has resulted in a small number of long-lasting remissions in patients with metastatic melanoma. In two consecutive phase II trials in a total of 67 patients, we assessed the potential synergism between both modalities, i.e. chemo- and immunotherapy. Treatment consisted of intravenous (i.v.) carboplatin (CBDCA, 400 mg/m2) and dacarbazine (DTIC, 750 mg/m2) given twice (i.v. bolus over 30 min) at 3-week intervals, or 4 cycles of DTIC (220 mg/m2 i.v. 3 days), cisplatin (DDP, 35 mg/m2 i.v. 3 days), carmustine (BCNU, 150 mg/m2 i.v. cycles 1 and 3) and tamoxifen (TAM, 20 mg oral/daily) at 3-week intervals. Chemotherapy was followed by immunotherapy with combined subcutaneous (s.c.) interleukin-2 (rIL-2) and SC interferon-alpha 2 (rIFN-alpha). Among 40 patients who received a full cycle of chemotherapy with CBDCA/DTIC and sequential immunotherapy, there were 3 (7.5%) complete remissions (CRs) with a median duration of 19 months (range 13-26+). Partial remissions (PRs) were noted in 11 (27.5%) patients with a median response duration of 8 (range 5-14) months. Among 27 patients who received DTIC/DDP/BCNU/TAM and rIL-2/rIFN-alpha, there were 3 (11%) complete remissions and 12 (44.5%) partial remissions. Duration of complete and partial remissions ranged from 9+ to 13+ (median, 11+), and 5 to 15+ (median, 7+) months, respectively. Chemotherapy produced mostly moderate toxicity. Thrombocytopenia was common with the nadir after a median time of 18 days following start of CBDCA/DTIC and DTIC/DDP/BCNU, respectively. 10 patients required transfusion of thrombocytes. Nausea and vomiting due to chemotherapy were well tolerated using concomitant ondansetrone (8 mg i.v.). Immunotherapy was self-administered at home with mild to moderate side effects; malaise, fever, chills, nausea/vomiting, diarrhoea, anorexia and arthralgias were most frequent, but were spontaneously reversible after ending rIL-2/IFN-alpha. A mean 87 and 88% of the projected doses of rIL-2 and rIFN-alpha were administered on either protocol. There were no life-threatening complications and no treatment-related deaths. The sequential combination of chemotherapy and rIL-2 plus rIFN-alpha had at least additive therapeutic activity against metastatic malignant melanoma. The schedules produced long-lasting remissions and were tolerated well overall. These trials substantiate a potential role for low to intermediate dose immunotherapy in maintaining and consolidating therapeutic effects of chemotherapy in metastatic melanoma.

Administration, Cutaneous↗