orabase and Multiple-Sclerosis

Interferon (IFN) responses to polyriboinosinic acid polyribocytidylic acid in poly-L-lysine and carboxymethylcellulose (poly ICLC) have been studied in detail in 6 men and 3 women as part of a preliminary trial in patients with multiple sclerosis (MS). Patients received intravenous (i.v.) doses of 100 micrograms/kg poly ICLC, and serum IFN levels were determined serially every 4 h for 16 h. Men and women produced substantial levels of IFN at 8, 12, and 16 h after infusion, but levels in men were consistently and significantly higher (p less than 0.05). Interferon responses were examined also in 3 male and 3 female Rhesus monkeys. Serum samples were obtained 8 and 24 h after i.v. injections of 1 mg/kg of poly ICLC. Again, there were significantly higher levels of IFN in males. The observed differences may reflect sex-linked differences in either drug metabolism or specific sensitivity to IFN induction by poly ICLC. The most interesting possibility is that the difference is due to a more general difference in IFN response between males and females. Studies are currently in progress to evaluate these possibilities.

Topics: Adult; Animals; Carboxymethylcellulose Sodium; Drug Evaluation, Preclinical; Female; Humans; Interferon Inducers; Interferons; Macaca mulatta; Male; Middle Aged; Multiple Sclerosis; Poly I-C; Polylysine; Sex Characteristics

Interferon (IFN) responses to polyriboinosinic acid polyribocytidylic acid in poly-L-lysine and carboxymethylcellulose (poly ICLC) have been studied in detail in 6 men and 3 women as part of a preliminary trial in patients with multiple sclerosis (MS). Patients received intravenous (i.v.) doses of 100 micrograms/kg poly ICLC, and serum IFN levels were determined serially every 4 h for 16 h. Men and women produced substantial levels of IFN at 8, 12, and 16 h after infusion, but levels in men were consistently and significantly higher (p less than 0.05). Interferon responses were examined also in 3 male and 3 female Rhesus monkeys. Serum samples were obtained 8 and 24 h after i.v. injections of 1 mg/kg of poly ICLC. Again, there were significantly higher levels of IFN in males. The observed differences may reflect sex-linked differences in either drug metabolism or specific sensitivity to IFN induction by poly ICLC. The most interesting possibility is that the difference is due to a more general difference in IFN response between males and females. Studies are currently in progress to evaluate these possibilities.

Topics: Animals; Carboxymethylcellulose Sodium; Clinical Trials as Topic; Female; Humans; Interferon Inducers; Interferons; Kinetics; Macaca mulatta; Male; Methylcellulose; Multiple Sclerosis; Poly I-C; Polylysine; Sex Factors

An open Phase I trial of poly(I,C)-LC in multiple sclerosis was conducted. Serious temperature elevations were typical and associated with transient accentuation of neurological dysfunction which required intensive nursing care, but no permanent complications to the treatment were observed. A regimen was developed for management of the side effects and reducing patient discomfort. Although there was a suggestion of stabilization of the disease in some patients, a conclusion about efficacy cannot be reached without a controlled trial. Future use of poly(I,C)-LC in multiple sclerosis should be confined to experimental trials in a research setting.

Topics: Carboxymethylcellulose Sodium; Clinical Trials as Topic; Female; Follow-Up Studies; Humans; Interferon Inducers; Interferons; Male; Methylcellulose; Multiple Sclerosis; Poly I-C; Polylysine

To investigate the cellular immune effects of the interferon inducer, Poly ICLC, in humans, peripheral blood mononuclear cells from patients with multiple sclerosis receiving Poly ICLC as part of a preliminary clinical trial were studied. Peripheral blood mononuclear cell phenotype analysis using fluoresceinated monoclonal antibodies and flow microfluorometry showed decreases in the percentages and absolute numbers of all lymphocyte subsets 24 h after infusion. These changes returned toward baseline at 48 h except the percentage of CD-4 positive cell which increased above baseline levels. The percentage of HLA-DR antigen positive cells and CD-16 (Leu 11a) positive cells were increased 24 h after infusion but returned to baseline at 48 h. NK activity as determined by chromium release from K562 target cells was decreased at 24 h but increased 48 h after drug infusion. The increases in percentages of HLA-DR antigen and CD-16 positive cells at 24 h and NK activity at 48 h are consistent with the in vitro effects of IFN while the decreases in peripheral blood mononuclear cells are suggestive of changes in cell recirculation.

Topics: Antigens, CD; Carboxymethylcellulose Sodium; Cytotoxicity, Immunologic; Drug Evaluation; Female; Flow Cytometry; HLA-DR Antigens; Humans; Immunity, Cellular; Killer Cells, Natural; Leukocytes, Mononuclear; Male; Multiple Sclerosis; Poly I-C; Polylysine; Time Factors

Although gamma interferon (gamma-IFN) may be involved in the pathogenesis of exacerbations of multiple sclerosis (MS), whether it plays a role in chronic progressive MS is not known. To investigate this, we retrospectively analyzed serum samples from nine chronic progressive MS patients who were treated with monthly intravenous infusions of the interferon inducer polyinosinic acid polycytidylic acid polylysine in carboxymethylcellulose (poly ICLC). Using a bioassay we found that the mean peak total interferon level was 177 U/ml 12 hours after infusion, and using a radioimmunoassay we found that the mean peak gamma-IFN level was 15.9 U/ml 12 hours after infusion, so that gamma-IFN made up approximately 10% of the total. Greater gamma-IFN induction did not correlate with clinical worsening; induced gamma-IFN levels were not higher in two patients who worsened on treatment, and the highest levels were found in a patient who remained stable. Either chronic progressive MS is not sensitive to gamma-IFN or the effects of gamma-IFN are masked by other mediators induced by poly ICLC.

Topics: Antigens, CD; Antigens, Differentiation; Carboxymethylcellulose Sodium; Chronic Disease; Female; HLA-DR Antigens; Humans; Infusions, Intravenous; Interferon Inducers; Interferon-gamma; Male; Multiple Sclerosis; Poly I-C; Polylysine; Receptors, Fc; Receptors, IgG; Retrospective Studies

Because interferon injections have recently been reported to induce cortisol in cancer patients, we retrospectively reviewed cortisol levels obtained during a preliminary trial of the interferon inducer polyriboinosinic polyribocytidylic acid in poly-L-lysine and carboxymethylcellulose (poly ICLC) in multiple sclerosis patients to determine if significant cortisol induction occurred. Analysis of data from 51 poly ICLC infusions in 6 men and 4 women showed elevated cortisol levels 4 to 16 hours after infusion, with hematological changes consistent with steroid effect. The highest cortisol levels observed were in 2 patients who improved during the treatment period, but there was no clear relationship between cortisol levels and clinical outcome in the group as a whole.

Topics: Adult; Carboxymethylcellulose Sodium; Female; Humans; Hydrocortisone; Interferon Inducers; Interferons; Male; Methylcellulose; Middle Aged; Multiple Sclerosis; Poly I-C; Polylysine; Retrospective Studies

A preliminary trial of the interferon (IFN) inducer polyriboinosinic acid-polyribocytidylic acid in poly-L-lysine and carboxymethylcellulose (poly ICLC) was conducted in patients with chronic progressive multiple sclerosis (MS). Because IFN induction in men is greater than in women, the kinetics of IFN induction were studied. As no significant differences were found in the serum half-life of IFN, sex-linked differences in IFN clearance or degradation are not likely to be responsible for the differences noted. Because fever was the major limiting side effect in MS patient, the relationship of fever to IFN levels was assessed. Changes in temperature were not related to changes in IFN levels, suggesting that fever might be blocked without reducing IFN levels.

Topics: Carboxymethylcellulose Sodium; Female; Humans; Hydrocortisone; Interferon Inducers; Interferons; Kinetics; Male; Methylcellulose; Multiple Sclerosis; Poly I-C; Polylysine

Eighteen patients with chronic progressive multiple sclerosis (MS) were treated in an open preliminary trial of the interferon inducer and immune modulator, poly ICLC. All patients produced substantial interferon levels and experienced acute side effects, including fever and transient worsening of neurologic symptoms. Of nine patients with rapid neurologic deterioration at the time of entry into the study, only three had disease progression during treatment. We conclude that poly ICLC can be administered safely to MS patients, and that a controlled trial will be necessary to determine efficacy.

Topics: Adult; Carboxymethylcellulose Sodium; Female; Humans; Interferon Inducers; Male; Methylcellulose; Middle Aged; Multiple Sclerosis; Poly I-C; Polylysine

Topics: Adult; Carboxymethylcellulose Sodium; Humans; Interferons; Liver; Male; Methylcellulose; Multiple Sclerosis; Poly I-C; Polylysine

Multiple sclerosis is a debilitating disease that is the focus of study in many clinical settings. In one center conducting research on multiple sclerosis, an investigational drug being studied is called polyinosinic-polycytidylic acid poly-l-lysine (Poly-ICLC). The role of the primary nurse in this research project is described and discussed. A case presentation is included to illustrate how a patient receives continuity of professional nursing care while participating in a research protocol.

Topics: Adult; Ambulatory Care; Carboxymethylcellulose Sodium; Female; Hospitals; Humans; Multiple Sclerosis; Patient Discharge; Poly I-C; Polylysine; Primary Nursing; Research