inosine-pranobex and Immunologic-Deficiency-Syndromes

Topics: Allergy and Immunology; Animals; Cell Differentiation; Disease Susceptibility; Drug Interactions; Humans; Immune System; Immunologic Deficiency Syndromes; Immunologic Factors; Inosine Pranobex; Interleukins; Levamisole; Neoplasms; Pharmacology; Signal Transduction; T-Lymphocytes; Thymus Hormones; Toxicology

The immunopharmacologic effects of Isoprinosine (INPX) have been associated with clinical benefit to the patient in a number of conditions characterized by immunodeficiency of diverse etiology. Immunodepressed homosexuals at risk of developing acquired immunodeficiency syndrome (AIDS) treated with placebo or INPX experienced an increase in the function and number of immunocompetent cells associated with clinical improvement. A multicenter trial designed to confirm these results has demonstrated that INPX produced an increase in natural killer (NK)-cell activity, total T cells, and T-helper cells, with certain effects persisting for months after completion of the 28-day treatment period. INPX-treated patients also experienced clinical improvement and decreased incidence of progression to AIDS. The administration of INPX for longer periods to patients with frank AIDS under a compassionate-use protocol has also proved useful. Clinical benefit associated with INPX treatment has been demonstrated in other patients with a depressed immune response, such as aged patients, cancer patients, severely burned patients, ill patients, and surgery patients. This program of clinical trials supports the therapeutic use of INPX in the treatment of AIDS and other acquired immunodeficiencies of clinical importance.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Humans; Immunologic Deficiency Syndromes; Inosine; Inosine Pranobex

Secondary immune deficiency generally involves more profound defects in cellular than humoral immunity. This type of immune deficiency occurs in acquired immunodeficiency syndrome (AIDS), cancer, malnutrition, aging and following immunosuppressive therapy. Immunorestorative therapies were developed for use in the immunotherapy of cancer. Their experimental use in cancer and other diseases such as infections and autoimmunity has demonstrated their safety and their capacity to improve host responses to disease particularly when the host is immunocompromised. Biologicals such as the thymic hormones and interferon have been intensively studied and are briefly reviewed in this paper. Chemically defined drugs such as levamisole, isoprinosine, azimexon, and muramyl dipeptides have also been extensively analyzed and the action of certain purine-related compounds are discussed to exemplify their immunopharmacologic features. The combined uses of biologicals and drugs are suggested to improve the efficiency of immunotherapy.

Topics: Humans; Hypoxanthines; Immunologic Deficiency Syndromes; Immunotherapy; Inosine Pranobex; Interferons; Interleukin-2; Purines; Thymosin; Thymus Extracts; Thymus Hormones; Transfer Factor

Topics: Adjuvants, Immunologic; Bacterial Vaccines; BCG Vaccine; Bone Marrow Transplantation; Cyclosporins; Fetus; Humans; Immune Sera; Immune Tolerance; Immunization; Immunization, Passive; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Immunotherapy; Injections, Intramuscular; Injections, Intravenous; Inosine Pranobex; Interferons; Leucine; Levamisole; Liver; Major Histocompatibility Complex; Plasma Exchange; Plasmapheresis; Propionibacterium acnes; Thymus Gland; Thymus Hormones; Transfer Factor; Tuftsin

Topics: Ascorbic Acid; Bone Marrow Transplantation; Fetus; Humans; Immunoglobulin G; Immunologic Deficiency Syndromes; Inosine Pranobex; Levamisole; Liver Transplantation; T-Lymphocytes; Thymus Gland; Thymus Hormones; Transfer Factor

Immunodepression associated with a variety of situations such as cancer or any of its major modalities of treatment (surgery, irradiation, or chemotherapy) has been effectively alleviated with Imunovir (inosine pranobex-BAN), and this has been associated with demonstrable clinical benefit to these patients. One hundred and six immunodepressed patients with solid tumors undergoing radiotherapy were treated with either Imunovir or placebo; 64% of Imunovir-treated patients were immunorestored after 3 months compared to 23% in the placebo group. Imunovir was also effectively used in 75 patients with malignant hematological disorders both as an immunorestorative agent given prophylactically to prevent infection and as a therapeutic agent to treat infections in these immunodepressed patients. In different studies involving surgical patients treated with either Imunovir or placebo, 70-81% of hypoergic or anergic patients in the Imunovir group became normoergic by day 14 of treatment compared to 5-17% of the placebo group, and this enhanced immunorestoration was associated with lower incidence of local sepsis (P less than 0.05), systemic sepsis (P less than 0.025), and postoperative mortality (P less than 0.05).

Topics: Female; Humans; Hypersensitivity, Delayed; Immune Tolerance; Immunologic Deficiency Syndromes; Inosine; Inosine Pranobex; Neoplasms

In a double-blind clinical trial, 61 immunodepressed males with persistent generalized lymphadenopathy (PGL) received one of two doses (1 or 3 g/day) of the immunomodulating drug inosine pranobex (INPX) or placebo for a period of 28 days. In the high-dose group, clinical improvement was reported by 11 of 21 patients (52%), within 5 months of the cessation of treatment. In contrast, 3 of 19 patients (16%) in the placebo group reported clinical improvement by that time. Patients receiving 3 g/day INPX showed a significant increase in NK cell activity by Day 14 and this elevation was still evident at the last follow-up examination 1 year after treatment. Increases in total T lymphocytes (T-11) and the percentage of T helper cells (T-4) were also observed. These responses were delayed and reached their peaks 2 months after the termination of drug treatment. The kinetics of these effects suggest that INPX stimulates the production of precursor cells and initiates a cascade of lymphocyte differentiation capable of producing long-term restoration of cell-mediated immunity. These data indicate that INPX may be beneficial to patients with PGL.

Topics: Antigens, Surface; Clinical Trials as Topic; Double-Blind Method; Homosexuality; Humans; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Immunotherapy; Inosine; Inosine Pranobex; Killer Cells, Natural; Male; Phenotype; Risk; T-Lymphocytes

Topics: Adolescent; Adult; Child; Female; Humans; Immune System; Immunologic Deficiency Syndromes; Inosine Pranobex; Male

Patients with various conditions associated with immunologic deficiency (cancer, radiotherapy, surgery, burns, aging, prodromal Acquired Immunodeficiency Syndrome, were treated with inosiplex (INPX) at a dose of 3-4 g/day for periods of time ranging from 1 week to several months. Patients were evaluated clinically, and immunologically with the following assays; natural killer (NK) cytotoxicity, T-lymphocyte count, mitogen-induced proliferation, E rosettes, and skin test reactivity. The data resulting from this large and varied population were quite consistent and reproducible, and indicated that INPX treatment was effective in simultaneously reducing the incidence of complications, infections and mortality while enhancing the immune status of the patient. It has therefore been concluded that an immunopharmacologically active agent such as INPX can elicit important clinical benefits in patients with disorders of diverse etiology, perhaps through modulation of an immunologic defect that is common to a variety of seemingly unrelated conditions.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Antineoplastic Agents; Burns; Humans; Immunity; Immunologic Deficiency Syndromes; Inosine; Inosine Pranobex; Kinetics; Middle Aged; Models, Biological; Neoplasms; Postoperative Complications

A hypothesis is put forth describing a role in immune regulation for inosine biosynthesis in the anticodon of tRNA. The enzymatic insertion of hypoxanthine into the tRNA wobble base position is predicted to be a control point for the translation of proteins and peptides required for normal immune function. The substrate for inosine biosynthesis in tRNA, hypoxanthine, is an intermediate in the purine catabolic pathway, and defects in this pathway are associated with inherited immunodeficiency diseases. Therefore, a role for aberrant inosine biosynthesis in tRNA is postulated in causing the immunodeficient conditions, and it may be a relevant molecular defect in leukemia as well.

Topics: Antibody Formation; Anticodon; Bone Marrow; Chromatography, High Pressure Liquid; Codon; Enzymes; Gene Expression Regulation; Humans; Hypoxanthine; Hypoxanthines; Immunity, Cellular; Immunocompetence; Immunologic Deficiency Syndromes; Inosine; Inosine Pranobex; Protein Biosynthesis; RNA, Transfer

Nine patients with alopecia totalis and associated defects in T lymphocyte function were admitted to an open-label trial of inosiplex therapy. All nine developed enhanced T cell function and seven had clinically significant hair regrowth. The immunologic response to inosiplex was dose-dependent in five patients. These data provide new information on the in vivo effects of inosiplex on the human immune system and support the hypothesis that disturbances of immunologic mechanisms may play a pathogenetic role in alopecia totalis in certain patients.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Alopecia; Female; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Inosine; Inosine Pranobex; Lymphocyte Activation; Male; Middle Aged; Rosette Formation; T-Lymphocytes

Equine lymphocytes incubated with Con A and isolated on discontinuous BSA density gradients suppressed mixed lymphocyte reactions in a cell dose- and Con A dose-dependent manner. Suppressor lymphocytes were radiosensitive, even after the initial Con A incubation phase was completed. Suppressor activity was consistently demonstrated using peripheral blood mononuclear leukocytes from normal horses, but was absent in thymus cells and variably present in lymph node cells. Suppressor lymphocytes were present in horses with selective IgM deficiency, and within neoplastic lymph nodes from a horse with lymphosarcoma and concomitant IgM deficiency. Suppressor cells were not detected in 5 of 6 horses with severe combined immunodeficiency.

Topics: Animals; Cell Separation; Concanavalin A; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Dysgammaglobulinemia; Horse Diseases; Horses; Humans; Immunoglobulin M; Immunologic Deficiency Syndromes; Inosine Pranobex; Lymphocyte Culture Test, Mixed; Lymphoma, Non-Hodgkin; T-Lymphocytes, Regulatory

The reason for giving substances with immunostimulatory properties is to restore or normalize immune functions. Since various human pathogenic viruses can induce immunodepression, the administration of immunostimulants offers a possibility for therapeutic intervention in the immune system. This could be demonstrated. Various virus infections can effectively be influenced by the synthetic immunostimulating agent Inosine Pranobex.

Topics: Antibody Formation; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Zoster; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Inosine; Inosine Pranobex; Male; Subacute Sclerosing Panencephalitis; Virus Diseases

The authors investigated the state of immunity, before and after surgery, in a group of 6 methisoprinol-treated patients and in a 10-patient control group both affected by malignant neoplasia. All the patients exhibited various degrees of immuno-depression. Versus the control group the group treated with 1-g methisoprinol injections at the dosage of 4 g daily for 7 days after surgery showed a positive effect on post-surgical immuno-depression.

Topics: Humans; Immunologic Deficiency Syndromes; Inosine; Inosine Pranobex; Neoplasms; Postoperative Complications; Surgical Procedures, Operative

Progressive vaccinia is a rare and serious complication of smallpox vaccination. Depressed immune function can generally be found as an underlying disorder; thus adequate immuno-correction may be expected to be therapeutically effective. Humoral and cell-mediated immunity was repeatedly examined in one case throughout the course of the disease. Results indicated partial deficiency of cell-mediated immunity. No therapeutic effect was achieved by using human antivaccinia immunoglobulin and N-methylisatin beta-thiosemicarbazone. Transfer factor therapy was also attempted. Treatment with a non-specific transfer factor preparation was followed by a transitory clinical improvement. A specific transfer factor preparation given during the last month of life, however, had no therapeutic effect. The patient died on the 145th day after vaccination. Autopsy findings pointed to combined immune deficiency.

Topics: Humans; Immunoglobulins; Immunologic Deficiency Syndromes; Infant; Inosine Pranobex; Male; Smallpox Vaccine; Thiosemicarbazones; Transfer Factor; Vaccinia