inosine-pranobex and AIDS-Related-Complex

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

Topics: AIDS-Related Complex; Antibodies, Viral; Double-Blind Method; HIV; HIV Antibodies; Humans; Inosine; Inosine Pranobex

We have evaluated the immunomodulatory effects of isoprinosine in a double blind randomized clinical study on 63 immunosuppressed male homosexuals with persistent generalized lymphadenopathy (PGL) or ARC. The subjects received either placebo or isoprinosine at 1 or 3 g/day for 28 days. All subjects were monitored for performance for a one year period. In the 3 g/day treatment group clinical improvement was reported by 52% of the patients in contrast to 15% in the placebo group. Patients receiving 3 g/day isoprinosine showed significant increase in NK cells, a major subset of which bears the Leu 7 surface antigen, and in NK cell function as early as at the termination of treatment. This normalized NK cell property was still evident 5 months after cessation of therapy. Total T lymphocytes and T helper cells also increased in this group and a concomitant reduction was observed in activated T lymphocytes (HLA-DR+). As a direct result of the therapy an increase was found in the Th regulatory (Leu 3+ Leu 8+) cell population resulting in normalization of Th inducer/Th regulatory cell ratio. A concomitant reduction to normal range occurred in Ts effector (Leu 2+ Leu 8-) and functionally activated Ts (Leu 2+ HLA-DR+) cell populations. The kinetics of these effects suggest that isoprinosine stimulates the production of precursor lymphocytes and initiates a process of cell differentiation capable of producing long-term restoration of host immunity.

Topics: Acquired Immunodeficiency Syndrome; Adjuvants, Immunologic; Adult; AIDS-Related Complex; Clinical Trials as Topic; Double-Blind Method; Humans; Inosine; Inosine Pranobex; Killer Cells, Natural; Male; Random Allocation; Risk Factors; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Topics: AIDS-Related Complex; CD4 Antigens; HIV Infections; Humans; Inosine Pranobex; Lymphocytes

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Humans; Immunity, Cellular; Inosine Pranobex; Interferons; Interleukin-2; Plasma Exchange

In patients with AIDS, LAS and ARC a defect in producing lymphokines such as Interleukin 2 and Gamma-interferon is found. Possibilities of therapy are reported. Especially the immunostimulant properties of inosiplex are commented, and the first successful results of therapy are discussed.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; B-Lymphocytes; Humans; Immunotherapy; Inosine; Inosine Pranobex; Interleukin-2; Models, Biological; T-Lymphocytes

Peripheral blood leukocytes from ARC and AIDS patients were analyzed following phytohemagglutinin- and pokeweed mitogen-induced lymphocyte transformation by dual-color flow cytometry using monoclonal antibodies that identify developmental (HLA-DR) and functional (Leu8) subsets of T cells and monocytes. Significant decreases in both the suppressor regulating helper T subset (Leu3+ Leu8+) and the reciprocal inducer helper T subset (Leu3+ Leu8-) responsible for inducing differentiation of B cells were observed. Simultaneously, the percentages of the effector suppressor T cells and the precursor suppressor T cells were increased, both of which were required for generation of suppression of cell-mediated immunity. There was also a progressive selection of Ia+ cells bearing the Leu2 (Ts) markers and a concurrent reduction of the percentage of antigen-presenting monocytes and activated helper T cells. These results suggest that the functional deficiencies in AIDS may be caused by defects in T-cell activation as well as antigen presentation by monocytes. Isoprinosine induced an increase in both regulator Th (Leu3+ Leu8+) and inducer Th (Leu3+ Leu8+) subsets of helper T cells while potentiating the expression of Ia antigen on helper T cells and monocytes during mitogen-driven DNA synthesis. These events initiated a cascade of cellular interactions leading to partial restoration of cell-mediated immune responses. These interferences with the defective helper/suppressor regulatory pathways may have important therapeutic implications.

Topics: Acquired Immunodeficiency Syndrome; Adjuvants, Immunologic; Adult; AIDS-Related Complex; Antigen-Presenting Cells; Antigens, Differentiation, T-Lymphocyte; B-Lymphocytes; Histocompatibility Antigens Class II; Humans; Inosine; Inosine Pranobex; Leukocytes, Mononuclear; Lymphocyte Activation; Lymphocyte Cooperation; Male; Middle Aged; T-Lymphocytes; T-Lymphocytes, Helper-Inducer

Isoprinosine and Imuthiol are non mitogenic immunomodulators active on T cell differentiation. In ARC patients, they modulate the circulating T cell receptor complex in terms of OKT4+ phenotype induction. This effect is not responsible for any expansion of the target population but for a partial inhibition of in vitro infection with LAV/HTLV III viral particles. At a clinical level, this means that these drugs may prove helpful in ARC patients when the virus has infected only a few helper cells.

Topics: Adult; AIDS-Related Complex; Ditiocarb; HIV; Humans; Inosine; Inosine Pranobex; Lymphocyte Activation; Male; Middle Aged; T-Lymphocytes