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Biomedical subjects

B Storer

Publications and source records attributed to B Storer.

At least 73 records · Page 4Linked to original sources
PubMed1990

Depressed in vitro T cell responses concomitant with augmented interleukin-2 responses by lymphocytes from cancer patients following in vivo treatment with interleukin-2.

Peripheral blood lymphocytes obtained from cancer patients receiving interleukin-2 (IL-2) on two separate clinical protocols were evaluated for their in vitro responses to IL-2, alloantigens, and PHA. IL-2 in vivo induced enhanced in vitro proliferative responses to IL-2 and diminished in vitro proliferative responses to phytohemagglutinin (PHA) and alloantigens. Alloinduced cytotoxic T cell responses were also depressed following in vivo IL-2. We examined the kinetics of the in vitro proliferative response to PHA and IL-2 and found that while the response of lymphocytes primed in vivo with IL-2 to PHA was depressed at all times during the 2 week in vitro exposure, the response to IL-2 peaked earlier and higher than did the response to IL-2 by lymphocytes obtained prior to IL-2 therapy. These contrasting effects on antigen-induced T cell responses vs. IL-2 induced nonspecific proliferative and cytotoxic responses suggest the importance of dose and timing of IL-2 administration when used to enhance antigen-specific T cell responses or as an immune enhancing agent combined with vaccines.

Cell Division↗
PubMed1990

Effects of combinations of interferon-beta ser and interferon-gamma on interferon-inducible proteins and on the cell cycle.

SKCO 1 human colon carcinoma cells have been shown to be synergistically inhibited in their growth by the combinations of alpha-interferon (IFN-alpha) or beta-interferon (IFN-beta ser) and gamma-interferon (IFN-gamma). To determine if a correlation could be established between this synergistic antiproliferative effect and a synergistic induction in IFN-inducible proteins, or a unique perturbation in the cell cycle, we studied the effects of IFN-beta ser and IFN-gamma, alone and in combination, on 2',5'-oligoadenylate (2-5A) synthetase, indoleamine-2,3-dioxygenase (IDO), a human analogue of the murine Mx protein (p78), and the phases of cell cycle. 2-5A synthetase was maximally induced after a 24-h exposure to both IFN-beta and IFN-gamma. A synergistic enhancement of 2-5A synthetase activity was observed only with low concentrations of each IFN (0.05 ng/ml). IDO activity was induced by IFN-gamma and the combination of IFN-beta ser and IFN-gamma, but not IFN-beta ser alone. The differences in IDO activity between IFN-gamma and the combination, however, were not statistically significant. The p78 protein was induced in a dose-dependent manner by IFN-alpha and IFN-beta ser. IFN-gamma enhanced the expression of p78 induction by IFN-alpha or IFN-beta ser, even at concentrations of IFN-gamma that did not induce the protein when administered as a single agent. The combination of IFN-alpha and IFN-beta ser, which results in an antagonistic antiproliferative effect, also resulted in an antagonistic induction of p78. No changes in the cell cycle were observed following exposure to IFN-beta ser, IFN-gamma, or the combination, and treatment with IFN-gamma did not inhibit the accumulation of cells in G2M caused by colchicine. Thus, the synergistic antiproliferative effect produced by IFN-beta ser and IFN-gamma in SKCO 1 cells could not be correlated with a synergistic enhancement in 2-5A synthetase or IDO activity, or with a perturbation in the cell cycle. In contrast, the combination of IFN-gamma and IFN-alpha or IFN-beta ser synergistically enhanced the expression of p78 protein in these cells.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

Repetitive weekly cycles of interleukin 2: effect of outpatient treatment with a lower dose of interleukin 2 on non-major histocompatibility complex-restricted killer activity.

Fifteen patients with advanced malignancy who had failed conventional therapy were entered into a protocol consisting of 1 inpatient mo of repetitive weekly cycles of interleukin 2 (IL-2) at 3 x 10(6) units/m2/day by constant infusion for the first 4 days of each week. This was followed by IL-2 administered on an outpatient basis at the same schedule but at a dose of 1 x 10(6) units/m2/day for the next 1 to 6 mo. Nine patients had renal carcinoma, four had melanoma, and two had lymphoma. Thirteen patients completed the induction month, and ten patients completed greater than or equal to 1 mo of outpatient therapy. Only one patient had therapy discontinued because of toxicity due to IL-2. No major toxicities occurred during outpatient therapy. After 1 mo of IL-2 at 3 x 10(6) units/m2/day, profound changes similar to those previously documented were seen in peripheral blood lymphocyte (PBL) counts (4.7-fold increase), lymphokine-activated killer activity (16-fold increase), and the percentage of PBL with natural killer-associated markers including a 3.6-fold increase in the percentage of PBL expressing the Leu 19 (NKH-1) marker, a 3.7-fold increase in Leu 11 (FcIgGR), and a 3.0-fold increase in Leu 17 (OKT10). These indicators of IL-2 effect all remained elevated relative to the baseline at the end of 1 and 2 mo of outpatient therapy at the lower dose. However, lymphokine-activated killer activity and Leu 17 percentage were significantly reduced relative to the effect of the higher induction dose. PBL taken from patients while receiving maintenance therapy showed strong and rapid responses to IL-2 in vitro, confirming the in vivo effects of prolonged IL-2 treatment. Nevertheless, there were no complete or partial antitumor responses seen. This study demonstrates that an immunologically active dose of IL-2 can be given long term as outpatient therapy with tolerable toxicity and results in highly IL-2-responsive "primed" lymphokine-activated killer cells.

Adult↗
PubMed1989

Randomized phase II-III trial of combination beta and gamma interferons and etoposide and cisplatin in inoperable non-small cell cancer of the lung.

We observed major responses in two patients with adenocarcinoma of the lung who had received a combination of interferon (IFN)-beta and IFN-gamma, immediately followed by chemotherapy. To verify these observations, we initiated a prospective randomized phase II-III trial of etoposide and cisplatin, with or without IFN-beta and IFN-gamma, in patients with inoperable non-small cell lung cancer. Thirty-seven patients were randomized to receive either two cycles of chemotherapy or 6 weeks of IFN-beta plus IFN-gamma followed by two cycles of chemotherapy. Chemotherapy consisted of 60 mg of cisplatin/m2 on day 1 and 120 mg of etoposide/m2 on days 4, 6, and 8, repeated every 21 days. Patients who were randomized to the IFN plus chemotherapy arm received 200 micrograms of IFN-gamma and 30 x 10(6) U of IFN-beta three times per week for 6 weeks, followed by two cycles of chemotherapy. Three of 18 (17%) eligible patients in the chemotherapy arm and two of 18 (11%) patients in the combination arm had partial responses. All responses occurred while patients were receiving chemotherapy. Median survival was 190 days for the chemotherapy arm and 246 days in the combined modality arm, as estimated from Kaplan-Meier curves (P = .35). We observed no significant difference in subjective toxic effects between the two arms. We observed more hematologic toxicity during chemotherapy on the combined modality arm (P = .02). We conclude that pretreatment with IFN-beta and IFN-gamma does not enhance the efficacy of etoposide and cisplatin in this disease. Although the combined modality arm is relatively well tolerated, it does result in more chemotherapy-associated toxic effects. This study also exemplifies a hybrid phase II-III trial design, which is useful in allowing phase II results to be quickly incorporated into a phase III trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Phase I trial of human lymphoblastoid interferon with whole body hyperthermia in advanced cancer.

Laboratory studies have shown a potentiation of the biological effects of interferons (IFN) by elevated temperatures (39.5-40.5 degrees C). Based on such observations a Phase I clinical trial involving 17 cancer patients was conducted to assess the toxicity and biological effects of combining whole body hyperthermia (WBH) (40.5 degrees C for 75 min) and IFN. The study design incorporated a treatment schedule which allowed comparisons of WBH alone, to IFN administered i.m., to combinations of the two modalities. Human lymphoblastoid IFN was given for 6 days in weeks, 2, 4, and 6. At least 4 patients were entered at each of three IFN dose levels (1 x 10(6) units/m2; 3 x 10(6) units/m2; 10 x 10(6) units/m2). WBH was delivered on day 1 of week 1, day 6 of week 4, and days 4 and 6 of week 6. IFN was administered 1 h prior to WBH. The schedule used allowed for the development of tachyphylaxis to IFN-induced fever. Maximum temperatures were not significantly higher 24 h post-IFN/WBH than after a comparable number of days of human lymphoblastoid IFN alone. There was no statistically significant difference in toxicity assessments, hematological and hepatic blood parameters, serum IFN levels, or biological response modulation (i.e., 2',5'-oligoadenylate synthetase activity; beta 2-microglobulin levels; natural killer cell cytotoxicity, using K562 target cells and Chang cells) 24 h posttreatment between human lymphoblastoid IFN alone or combined modality therapy. No cumulative toxicity was observed in 6 patients receiving maintenance therapy for up to 1 year. Prior preclinical observations, together with the clinical safety reported in this study, encourage further investigation into the interactions between IFNs and hyperthermia.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

A pilot study of short-course, high-dose cytosine arabinoside, etoposide, and cisplatin in refractory, aggressive-histology, non-Hodgkin's lymphomas.

Twenty-three patients with refractory, aggressive-histology, non-Hodgkin's lymphomas were treated with cytosine arabinoside (2.0 g/m2 i.v. every 12 h on days 1 and 2), etoposide (100 mg/m2 i.v. on days 1 and 2), and cisplatin (35 mg/m2 i.v. on days 1 and 2) every 3 weeks. All patients had received one or two prior chemotherapy regimens. Five of 19 (26%) evaluable patients responded, with a median duration of response of 9 weeks (90% confidence interval: 11-48%). One patient with a complete response remains free of disease over 31 months after completing six cycles of therapy. Six transient responses of less than 1-month duration were also observed. Hematological toxicity was significant: 73% of patients experienced grade 4 neutropenia, and 52% experienced grade 4 thrombocytopenia. Twenty patients (87%) underwent dose reductions following their first cycle of therapy for grade 3 or 4 myelosuppression. We conclude that this combination of drugs, when administered by this schedule, has limited antitumor activity; however, administering the regimen with a dose-intense schedule appears warranted.

Adult↗
PubMed1989

Phase 1 clinical trial of recombinant interleukin-2: a comparison of bolus and continuous intravenous infusion.

The toxicologic, biologic, and clinical effects of recombinant interleukin-2 (IL-2) were tested in 25 patients with cancer. Escalating doses from 10(3) to 10(7) U/m2 per day were given by either daily bolus injection (BI) or continuous infusion (CI) for 7 consecutive days. Dose-limiting toxicities included a decline in performance status, systolic hypotension, and fever, which reversed promptly with discontinuation of therapy. The maximum tolerated dose of IL-2 by BI for 7 days was 3 X 10(6) U/m2 per day and for CI was 10(6) U/m2 per day. Significant changes in the number, phenotype, and function of circulating peripheral blood lymphocytes occurred at doses greater than or equal to 10(6) U/m2 per day by both administration schedules. With the initiation of therapy, a decline in the number of circulating peripheral blood lymphocytes (PBL) was seen in patients treated by either BI or CI. Additionally, the in vitro cytotoxic activity of these PBL against K562 was markedly decreased. Within 24 h of completing BI or CI, a rebound increase in the number of circulating PBL was seen. The phenotype of the circulating PBL after completion of treatment showed a significant (p greater than or equal to 0.05) increase in the numbers of OKT-3+, OKT-8+, OKT-10+, OK-Ia+, OKM1+, and OKT-11+ for patients treated by CI. Those patients treated by BI had a significant increase in Ia+ and OKT10+ cells. At IL-2 doses greater than or equal to 10(5) U/m2 per day, the PBL obtained following treatment with rIL-2 demonstrated in vitro cytotoxic capacity against K562 target cells that was significantly enhanced over pretreatment levels. This study demonstrates that IL-2 can be given by CI or BI in a non-ICU setting with acceptable dose-dependent toxicity. Upon completion of treatment an increase in the number of activated cells could be detected. Although no clinical responses occurred, the generation of endogenous activated PBL capable of enhanced cytotoxicity is encouraging. Future studies will explore the use of multiple courses of treatment with IL-2 to determine if therapeutic efficacy can be accomplished.

Antibodies, Monoclonal↗
PubMed1988

Repetitive weekly cycles of interleukin-2. II. Clinical and immunologic effects of dose, schedule, and addition of indomethacin.

Clinical trials with high doses of interleukin 2 (IL-2) have shown antitumor responses, but many of the patients have experienced severe and occasionally life-threatening toxic effects. Preclinical studies indicate that modifications in IL-2 dose, route, and schedule can influence both immune activation and antitumor effects. This study evaluated the clinical tolerance to and immunologic modifications induced by four repetitive weekly cycles of IL-2, with two dose levels (1 X 10(6) and 3 X 10(6) U/m2 per day) of IL-2 and three different daily administration schedules [bolus, continuous, or combined (bolus and continuous)], with and without indomethacin treatment. Patients in all treatment groups experienced acceptable, non-life-threatening toxic effects and immune system stimulation characterized by rebound lymphocytosis with increased numbers of natural killer and lymphokine-activated killer cells and enhanced direct cytolytic function. These immune changes were significantly enhanced by the repetition of IL-2 cycles beyond the first week of therapy. At an IL-2 dose of 3 X 10(6) U/m2 per day, bolus IL-2 was less immunostimulatory than continuous-infusion IL-2. The combined regimen (with half of each daily dose given as a bolus and half as a 24-hr infusion) was as stimulatory as continuous-infusion IL-2 and also induced antitumor effects. Finally, the addition of indomethacin to this regimen did not significantly modify in vitro or in vivo immune response parameters but appeared to worsen the systemic toxic effects of renal dysfunction and capillary leakage. These results suggest that continuous or combined infusion of IL-2 at 3 X 10(6) U/m2 per day on this schedule should be considered for further testing in phase II trials or in combination with other therapeutic modalities.

Adult↗
PubMed1988

Clinical and immunological effects of recombinant interleukin 2 given by repetitive weekly cycles to patients with cancer.

Eleven patients received four consecutive weekly cycles of human recombinant interleukin 2 (IL-2) by continuous infusion for 4 days/week. Two dose levels were tested, 1 and 3 X 10(6) units/m2/day. Toxicities experienced by most patients included fever, rigors, fatigue, anemia, eosinophilia, and liver function abnormalities. All side effects from treatment reversed and no severe or life-threatening problems occurred. A marked lymphocytosis was seen following the 4 weeks of therapy. Fresh lymphocytes obtained during this lymphocytosis mediated enhanced destruction in vitro of a natural killer cell-resistant tumor cell line (Daudi). The increase in the absolute number of circulating lymphocytes and their enhanced ability to mediate direct lysis of Daudi targets resulted in a greater than 100-fold mean increase in cytotoxic potential by the end of IL-2 treatment. One patient, with renal carcinoma, who was treated at 3 X 10(6) units/m2/day experienced a sustained measurable response with greater than 50% regression of pulmonary and hepatic metastases. Five patients were retreated with a second course of IL-2, lasting 4 weeks. This therapy was well tolerated in four of these five patients, with similar immunological changes occurring. No further antitumor responses were seen in these patients. Thus, a relatively well tolerated immunotherapy regimen using IL-2 can induce dramatic increases in lymphocyte number and augment their in vitro antitumor reactivity.

Cytotoxicity, Immunologic↗
PubMed1988

In vivo induction of the lymphokine-activated killer phenomenon: interleukin 2-dependent human non-major histocompatibility complex-restricted cytotoxicity generated in vivo during administration of human recombinant interleukin 2.

The availability of purified human recombinant interleukin 2 (IL-2) has enabled clinical trials to test its in vivo effects. We report here the immunological effects of 7 consecutive days of IL-2 treatment given to 25 patients with cancer in a clinical Phase I study. Peripheral blood lymphocytes obtained from patients following therapy with IL-2 had enhanced proliferative responses to IL-2 and enhanced direct cytotoxic activity on K562 target cells. This lytic activity was further augmented by the addition of IL-2 during the 51Cr release assay. Fresh peripheral blood lymphocytes from some patients who had just completed treatment at the higher IL-2 dose levels were able to kill both the natural killer-resistant Daudi cell line and fresh tumor cells while pretreatment samples and peripheral blood lymphocytes from healthy controls were not. This lytic activity was best detected when IL-2 was present in the in vitro effector assay. These results demonstrate that the administration of IL-2 to patients with cancer induces a population of effector cells able to directly destroy natural killer-resistant target cells, when assayed in the presence of IL-2.

Cells, Cultured↗
PubMed1988

Repetitive weekly cycles of recombinant human interleukin-2: responses of renal carcinoma with acceptable toxicity.

A phase I trial of repetitive weekly cycles of human recombinant interleukin-2 (IL-2) was performed in 23 patients with metastatic carcinoma. Patients received 4 days of IL-2 each week, followed by 3 days of observation, for 4 consecutive weeks. IL-2 was administered iv at 1.0 or 3.0 X 10(6) U/m2/day by one of three schedules involving continuous or bolus infusions. All treatment was carried out in a general hospital ward without intensive care unit monitoring or support. Seventeen patients had metastatic renal cell carcinoma; three of these demonstrated measurable (greater than 50% shrinkage) partial responses. This study demonstrates that IL-2 given alone without lymphokine-activated killer cells in this manner can induce antitumor effects with acceptable toxicity.

Adult↗
PubMed1988

Phase II trial of a combination of interferon-beta ser and interferon-gamma in patients with advanced malignant melanoma.

Based upon the in vitro synergistic activity of interferon-beta (IFN-beta) and interferon-gamma (IFN-gamma) observed in melanoma cells, we initiated a Phase II trial using the combination to determine the clinical antitumor efficacy in patients with advanced disease. Fifteen patients with metastatic malignant melanoma were given 2,000 micrograms of recombinant IFN-gamma (rIFN-gamma) (Biogen) intravenously (i.v.) over 10 min, followed by a 10 min i.v. injection of 30 million units of recombinant IFN-beta (rIFN-beta ser) (Triton) 3 x/week. Six patients had skin, soft tissue, nodal, or subcutaneous metastases, 6 had visceral disease only, and 3 had both. Seven patients had received prior treatment, including chemotherapy (6), radiotherapy (3), and/or immunotherapy (3). Side effects included typical IFN constitutional symptoms such as anorexia, fatigue, nausea, and myalgias, but were not dose limiting. The mean drop in the white blood cell count (WBC) following 1 month of therapy, compared to baseline, was 3.3 x 10(3)/mm2 (p = 0.002); the mean increase in SGOT was 24.1 U/l (p less than 0.001). One patient had a dose reduction for Grade III anorexia and fatigue which did not resolve with repeated treatment. One patient with liver metastases had radiographical and clinical stabilization of his disease for 1 year. No responses were seen. The median time to progression was 6 weeks. Two patients' tumors were evaluable in the human tumor colony forming assay (HTCFA) and were markedly sensitive to the antiproliferative effects of IFN combinations. Both patients, however, failed to respond clinically.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Effectiveness of smoking cessation interventions integrated into primary care practice.

Using a complete factorial design, we tested three interventions for smoking cessation in routine primary care practice. The interventions tested were 1) physician counseling, 2) mailed letters and educational materials designed by the National Cancer Institute (NCI), and 3) referral to smoking cessation classes. Thirty-seven family practice physicians at three of Group Health's outpatient facilities participated. Patient participation rates were 95%, and follow-up was complete for 92% of those participating. None of the interventions had any effect on point prevalence of quitting as determined 8-9 months later by self-report. However, the combination of physician counseling and NCI materials doubled the odds of occurrence of significant antismoking behavior (quit, quit and relapse, or cut down) during the ensuing 8-9 months in those individuals receiving that combination. Referral to smoking cessation classes was strikingly ineffective in this setting. Of 369 individuals designated by study design for referral, only 14% even investigated the classes. This compares with a 10% self-referral rate for those persons not designated for referral by our study design. Our results and other recent work suggest that more intensive interventions on multiple occasions based on relapse prevention strategies hold promise for future success in smoking cessation efforts in primary care.

Counseling↗
PubMed1988

The in vitro function of lymphocytes from 25 cancer patients receiving four to seven consecutive days of recombinant IL-2.

Twenty-five cancer patients received human recombinant interleukin-2 (IL-2) for 4 to 7 consecutive days in a Phase I trial. IL-2 was administered either as a daily intravenous bolus infusion (lasting 15 min), or as a continuous infusion lasting 24 h each day. Prior studies have demonstrated that in vivo administration of IL-2 at high doses is associated with changes in the phenotype of circulating peripheral blood lymphocytes (PBL) (determined with monoclonal antibodies), and the induction of augmented in vitro natural killer activity (NK) by PBL obtained following in vivo IL-2. We have noted that fresh lymphocytes obtained after 4-7 consecutive days of IL-2 (greater than or equal to 10(6) U/m2/day) show an augmented ability to kill NK-sensitive and -insensitive target cells (K562 and Daudi targets, respectively), especially when tested with IL-2 present during the 4-h 51Cr release assay. We have further analyzed lymphocytes in a battery of in vitro proliferative and cytotoxic assays. We present here the summary of this quantitative analysis of their responses in both antigen-specific and -nonspecific immune responses. Striking in vitro changes were observed in the proliferative response to IL-2 and in cytotoxicity stimulated by (or requiring) in vitro IL-2. Proliferative responses to antigens and to mitogens were not as dramatically altered following in vivo IL-2, nor were allospecific or allo-activated cytotoxic interactions. These studies indicate that the most striking changes in lymphocyte function measured in vitro following in vivo IL-2 are seen in those functions requiring IL-2.

Cytotoxicity, Immunologic↗
PubMed1987

Synergistic antitumor effects of tumor necrosis factor and gamma-interferon on human colon carcinoma cell lines.

We assessed the antiproliferative effects of tumor necrosis factor (TNF-alpha) and gamma-interferon (IFN-gamma) alone and in combination, on nine human colon carcinoma cell lines. All were resistant (less than 30% inhibition) to TNF-alpha alone. Four cell lines were resistant to IFN-gamma alone, two exhibited a minimal degree of sensitivity (30-50% inhibition), one was moderately sensitive, and two were inhibited 70% or greater. A synergistic antiproliferative effect occurred in eight of the nine cell lines treated with a combination of TNF-alpha and IFN-gamma. In seven of these eight, the combination of cytokines resulted in 30-40% more growth inhibition than predicted had an additive interaction occurred (P less than 0.005). In two cell lines with an induced resistance to mitomycin C, an increase in resistance to combined TNF-alpha and IFN-gamma treatment correlated with an increasing resistance to mitomycin C. The data were further analyzed to determine if combination treatment altered the sensitivity of the cells to one or both agents in addition to synergistically potentiating growth inhibitory effects. Combinations of TNF-alpha/IFN-gamma enhanced the dose response activity of TNF-alpha in three cell lines (P less than or equal to 0.09) and decreased the dose response activity of IFN-gamma in another three (P less than or equal to 0.02). Colony forming experiments on HCT 116 cells demonstrated a reduction in the number of 250-micron colonies in the IFN-gamma/TNF-alpha treatment groups when compared to controls, indicating that combined treatment had a cytotoxic effect. We conclude that combination TNF-alpha/IFN-gamma treatment has a synergistic cytotoxic effect on human colon carcinoma cells. IFN-gamma may enhance the effectiveness of TNF-alpha in some cell lines, but not conversely. These results may have therapeutic implications.

Cell Cycle↗
PubMed1987

Tissue-type plasminogen activator and streptokinase induce platelet hyperaggregability in the rabbit.

The ex vivo aggregability of rabbit platelets was assessed after rabbits were treated in vivo with thrombolytic doses of tissue plasminogen activator (t-PA) or streptokinase (SK). t-PA was evaluated at 2 doses; an effective thrombolytic dose of 10 micrograms/kg/min, i.v. and a higher dose of 30 micrograms/kg/min, i.v.. At both concentrations, ex vivo platelet hyperaggregability was observed when collagen, arachidonic acid or ADP were employed as the aggregating agonists. Significant falls in circulating platelet counts were observed after t-PA infusion. Infusion of SK also resulted in ex vivo platelet hyperaggregation. These data reveal that thrombolytic therapy may result in hyperaggregable platelets which may play a role in reocclusion of successfully recanalized blood vessels.

Adenosine Diphosphate↗
PubMed1987

Plasma lipoprotein changes in humans induced by beta-interferon.

Two groups of patients were administered either 4.5 X 10(6) U or 90 X 10(6) U each of recombinant DNA-derived interferon-beta serine (IFN-beta ser) i.v. daily for 10 days. IFN-beta ser affected lipoprotein lipids of patients in a dose dependent fashion. A decrease in plasma total cholesterol concentration occurred 24 h after therapy was initiated, regardless of dose. A dose-related decrease in plasma cholesterol concentration of 9% and 23% for patients on the low dose and high dose respectively occurred after 9 days of therapy. The plasma total cholesterol concentration decrease resulted primarily from a decrease in LDL cholesterol of 28% and 50% for patients on low and high doses respectively of IFN-beta ser. HDL-cholesterol was not significantly affected by IFN-beta ser administration. A dose-related increase in plasma triglyceride concentration occurred during IFN-beta ser, increasing 74% for patients on low dose and 136% for patients on high doses. This increase was only observed after 9 days on IFN-beta ser. Cholesterol reduction and triglyceride increases followed different time courses indicating different mechanisms may be involved.

Cholesterol↗