inosine-pranobex and Melanoma

Immunomodulatory effect of Isoprinosine are presented in melanoma and HTLV-III/LAV infected patients. Isoprinosine (50 mg/kg) was used as a pulse immunotherapy according to two different schedules: A) 5 days every 15 days and B) 5 days every 15 days for 2 months, then 5 days every 2 months. The patients' immunological profiles were tested before and during the treatment in terms of T-cell subsets, cell number requirement for PHA-induced proliferation, and delayed hypersensitivity reaction to recall antigens. Primary malignant melanoma patients are randomized between surgery alone or associated to isotherapy (schedule A or B). Schedule A, after an initial improvement of surgery-induced immune deficiency, is responsible for an immunodepression, whereas schedule B determines a prolonged restoration in immune responses in melanoma and AIDS related complex or Kaposi sarcoma patients as well. In vitro effects of Isoprinosine on HTLV-III/LAV infection are presented. These data exhibit 1) the need of an immunological follow-up during isotherapy and 2) the immunological benefit of a pulse immunotherapy during acquired immunodeficiencies related to cancer surgery or to HTLV-III/LAV infection in man.

Topics: Acquired Immunodeficiency Syndrome; Clinical Trials as Topic; Drug Administration Schedule; Humans; Immunotherapy; Inosine; Inosine Pranobex; Melanoma; Random Allocation

Addition of isoprinosine to cultures of blood mononuclear cells was shown to inhibit natural killer (NK) cell activity against the K562 myeloid cells and melanoma cells. This appeared to be due to inhibitory influences of monocytes in that after removal of adherent cells isoprinosine appeared to stimulate NK activity. Similar effects were noted on T cells separated by E rosette procedures. Administration of isoprinosine in vivo had variable effects on NK activity during drug administration but there was a significant increase in NK activity 3 days after cessation of the drug. These changes in NK activity may reflect different threshold levels of the drug on suppressor and NK cell populations and the relative proportions of different lymphocyte populations in individual subjects. Further studies with a wider range of drug doses and more frequent monitoring of responses are required to further evaluate the effect of isoprinosine on NK activity.

Topics: Adult; Chromium Radioisotopes; Cytotoxicity, Immunologic; Female; Humans; Immunosuppressive Agents; In Vitro Techniques; Inosine; Inosine Pranobex; Killer Cells, Natural; Male; Melanoma; Middle Aged; Monocytes; Rosette Formation

Isoprinosine appeared to potentiate the production of interleukin 1 and interleukin 2 in cultures of lipopolysaccharide stimulated human monocytes and phytohemagglutinin stimulated cultures of blood mononuclear cells respectively at pharmacological drug levels. Administration of the drug in vivo was associated with increased activity of radiation sensitive suppressor T cell activity against immunoglobulin production in pokeweed mitogen stimulated cultures of B and T cells. Addition of isoprinosine to the latter cultures in vitro appeared to enhance immunoglobulin production consistent with inhibition of suppressor cell activity or stimulation of helper activity. It is not clear from these studies whether the contrasting effects of the drug in vitro and in vivo represent different actions of metabolites or alteration of the proportion of lymphocyte subsets in the circulation. Further studies are required to answer these questions and to determine whether the changes persist with long term administration of the drug.

Topics: Adjuvants, Immunologic; Adult; B-Lymphocytes; Humans; Immunoglobulin G; Inosine; Inosine Pranobex; Interleukin-1; Interleukin-2; Lipopolysaccharides; Lymphocyte Activation; Male; Melanoma; Middle Aged; Pokeweed Mitogens; T-Lymphocytes, Regulatory