inosine-pranobex and Acquired-Immunodeficiency-Syndrome

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

Inosine pranobex is a synthetic compound formed from the p-acetamido benzoate salt of N-N dimethylamino-2-propanol and inosine in a 3:1 molar ratio. It has been reported to exert antiviral and antitumour activities in vivo which are secondary to an immunomodulating effect, and early results suggest beneficial clinical effects in several diseases and infections including mucocutaneous Herpes simplex infections, subacute sclerosing panencephalitis, genital warts, influenza, zoster, and type B viral hepatitis, as well as in homosexual men with persistent generalised lymphadenopathy. However, many of the studies have been preliminary in nature and deficient in design or in the reporting of their results. One must therefore conclude that while inosine pranobex may prove to be a valuable and innovative therapy for a number of diseases and infections for which no satisfactory therapy exist, further long term well controlled studies in larger numbers of patients are required before definitive conclusions about the efficacy of inosine pranobex in these disorders will be possible.

Topics: Acquired Immunodeficiency Syndrome; Adjuvants, Immunologic; Animals; Antineoplastic Agents; Antiviral Agents; Autoimmune Diseases; Humans; Inosine; Inosine Pranobex; Kinetics; Virus Diseases

The safety and efficacy of isoprinosine in HIV-infected individuals were assessed in a multicentre, randomized, double-blind, 24-week study phase, followed by an optional 24-week open treatment phase. The results of the double-blind phase have been reported separately. Of 866 HIV-seropositive individuals randomized, 832 were eligible for efficacy analysis. On completion of the double-blind phase, 596 patients started open treatment. All patients were evaluated with regard to progression to AIDS. Within 48 weeks, 10/412 patients (2.4%) assigned isoprinosine and 27/420 (6.4%) assigned placebo progressed to AIDS (p = 0.005; odds ratio: 2.8, 95% CI: 1.3-6.2). Intention-to-treat analysis showed identical results. No severe adverse reactions or toxicities were observed. We conclude that HIV-infected individuals without AIDS may be safely and effectively treated with isoprinosine.

Topics: Acquired Immunodeficiency Syndrome; Denmark; Double-Blind Method; HIV Infections; Humans; Inosine Pranobex; Sweden

The objective of this study was to evaluate the effect of isoprinosine on HIV-antigen expression in HIV-positive patients without AIDS.. Serum samples from anti-HIV-positive patients without AIDS participating in a double-blind, placebo-controlled trial of isoprinosine in the treatment of HIV infection were analysed for the presence of HIV antigen.. Data and samples were collected from the 21 medical centres who participated in the Scandinavian multicentre placebo-controlled isoprinosine study.. Samples were available from 19 of 21 participating centres. Of 866 patients who enrolled, baseline serum samples were available for 642 (74%; 308 isoprinosine- and 334 placebo-treated patients).. Treatment was 1 g isoprinosine administered orally three times a day or matching placebo for 24 weeks.. Comparison of HIV-antigen levels before and during treatment in both the isoprinosine-treated group and the placebo-treated group of patients.. During the study, AIDS developed in 19 patients; 17 of whom were receiving placebo treatment and two isoprinosine. The proportion of HIV-antigen-positive patients developing AIDS during treatment was significantly different from the proportion of HIV-antigen-negative patients in whom AIDS developed (6 versus 2%; P = 0.02). No significant changes in HIV-antigen levels were observed between the isoprinosine- and the placebo-treated group of HIV-antigen-positive patients. Median HIV-antigen levels did not change significantly in either the isoprinosine- or the placebo-treated group.. Our results suggest that isoprinosine does not have antiviral activity against HIV in vivo.

Topics: Acquired Immunodeficiency Syndrome; CD4-Positive T-Lymphocytes; Double-Blind Method; HIV Antigens; HIV Seropositivity; Humans; Inosine Pranobex; Leukocyte Count

The safety and clinical impact of isoprinosine in HIV-infected individuals were assessed in a multicentre, randomized, double-blind, 24-week study phase, followed by an optional 24-week open treatment phase. The results of the double-blind phase have been reported. Of 866 HIV-seropositive patients randomized, 832 subjects were eligible for efficacy analysis. On completion of the double-blind phase, 596 patients started open treatment. All patients were evaluated with regard to progression to AIDS and/or death. Within 48 weeks, 10/412 (2.4%) patients assigned isoprinosine and 27/420 (6.4%) patients assigned placebo progressed to AIDS (P = 0.005). Intention-to-treat analysis showed identical results. Viewing the open treatment phase in isolation revealed no difference in progression rates between those treated and those not receiving the drug, perhaps reflecting the higher proportion of patients receiving zidovudine or PCP prophylaxis in the latter group. No severe adverse reactions or toxicities were observed. We conclude that HIV-seropositive patients without AIDS may be safely and effectively treated with isoprinosine.

Topics: Acquired Immunodeficiency Syndrome; Double-Blind Method; Female; Follow-Up Studies; HIV Seropositivity; Humans; Inosine Pranobex; Male; Scandinavian and Nordic Countries; Survival Analysis; Time Factors; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Age Factors; Aged; HIV Infections; Humans; Inosine Pranobex; Middle Aged

We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of inosine pranobex (Isoprinosine) [corrected] in the treatment of patients with human immunodeficiency virus (HIV) infection but without manifest acquired immunodeficiency syndrome (AIDS). A total of 866 patients were enrolled in 21 centers in Denmark and Sweden. The patients were stratified in three groups according to their CD4+ cell count and randomly assigned to receive either inosine pranobex (1 g three times a day) (n = 429) or matching placebo (n = 437) for 24 weeks. Of the 831 patients who could be evaluated, AIDS developed in 17 in the placebo group as compared with 2 in the inosine pranobex group (P less than 0.001; odds ratio, 8.6 [95 percent confidence limits, 2.2 and 52.6]). There were no significant differences between the groups with respect to changes in CD4+ cell count or the development of other HIV-related conditions, with the exception of thrush, which developed in fewer patients in the inosine pranobex group (P = 0.05). No serious side effects were observed. We conclude that treatment with inosine pranobex delays progression to AIDS in patients with HIV infection. The duration of this beneficial effect, the optimal dose, and the mode of action of inosine pranobex remain to be clarified.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; CD4-Positive T-Lymphocytes; Double-Blind Method; HIV Infections; Humans; Inosine; Inosine Pranobex; Leukocyte Count; Middle Aged; Randomized Controlled Trials as Topic; T-Lymphocytes, Regulatory

Topics: Acquired Immunodeficiency Syndrome; Drug Evaluation; HIV; HIV Infections; Humans; Inosine; Inosine Pranobex; Randomized Controlled Trials as Topic

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Denmark; Double-Blind Method; HIV Seropositivity; Humans; Inosine; Inosine Pranobex; Middle Aged; Randomized Controlled Trials as Topic; Sweden

Topics: Acquired Immunodeficiency Syndrome; Follow-Up Studies; Humans; Inosine Pranobex; Scandinavian and Nordic Countries

Inosine-pranobex (methisoprinol, isoprinosine; INPX) is the p-acetamidobenzoic salt of N,N-dimethylamino-2-propanol and inosine in a 3:1 molar ratio. In early studies, INPX was found to partially inhibit human immunodeficiency virus (HIV) and to increase the immunocompetence of HIV-infected subjects in vitro. We report the results of a randomised, multicentric clinical trial carried out on 553 HIV+ patients. 261 individuals were treated with INPX (two 500 mg tablets every 6 h for 3 months) and the remaining 292 constituted the untreated control group. INPX treatment was associated with a slightly improved clinical condition or with a trend in that direction, as compared to the untreated group. A preservation of the CD4/CD8 cell ratio values, a decrease in the CD8+ cells and an increase in the Leu 2-7+ cell number better than in the untreated individuals was also observed in the patients taking INPX. No serious or adverse effects of INPX have been observed.

Topics: Acquired Immunodeficiency Syndrome; Adjuvants, Immunologic; Adult; Antiviral Agents; Blood Cell Count; Clinical Trials as Topic; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Inosine; Inosine Pranobex; Male; Multicenter Studies as Topic; Random Allocation

Twenty patients with Acquired Immune Deficiency Syndrome (AIDS) received treatment with Inosine Pranobex and specific antibacterial and anti-parasitic therapy. Five died shortly after hospitalization, but a further fifteen who also received ACTH, survived, gained weight and improved clinically, biochemically and haematologically.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adrenocorticotropic Hormone; Adult; Clinical Trials as Topic; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Inosine; Inosine Pranobex; Male; Middle Aged; Trinidad and Tobago

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

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: Acquired Immunodeficiency Syndrome; HIV Seropositivity; Inosine; Inosine Pranobex

Methisoprinol (isoprinosine) is a synthetic compound with reported antiviral and immunomodulating properties. Results of the present study showed that methisoprinol at concentrations greater than or equal to 200 micrograms/ml reduces the p24 and gp120 viral antigen expression on the surface of human immunodeficiency virus (HIV)-infected lymphocytes and the reverse transcriptase levels. In addition, cell viability, the number of the CD4+ cells, and the CD4+/CD8+ cell ratio are higher in methisoprinol-pretreated cell suspensions than in untreated HIV-infected cell cultures. A quantitative freeze-fracture study on the density of the intramembranous particles (IMP) present on both fracture faces of the plasma membrane of lymphocytes has shown that pretreatment with methisoprinol induces a different molecular organization resulting in a nearly three times increase of IMP density.

Topics: Acquired Immunodeficiency Syndrome; Adult; Cell Membrane; Cytopathogenic Effect, Viral; HIV; Humans; In Vitro Techniques; Inosine; Inosine Pranobex; Lymphocytes; Microscopy, Electron

Topics: Acquired Immunodeficiency Syndrome; Drug Administration Schedule; Drug Therapy, Combination; Humans; Inosine; Inosine Pranobex; Zidovudine

3'-azido-3'-deoxythymidine (AZT) was administered orally to 8 AIDS patients at a dose of 100 mg every 6 hours for 14 days. On days 8 - 14 the patients were also given 1 g inosine-pranobex (INPX) every 6 hours. On day 7, while the subjects were taking AZT alone and on day 14 while they were receiving AZT + INPX, blood samples were obtained over a 6-hour dosing interval for measurement of AZT by a specific AZT radioimmunoassay. AZT levels on day 14 were significantly higher than the corresponding levels on day 7, resulting in a 2-fold increase of the area under the serum concentration-time curve (AUC) and a prolongation of the mean half-life of AZT (44 to 70 min) during the INPX treatment. INPX is an immunomodulatory drug with an inhibitory effect on HIV. The potential advantages of a combined treatment AZT + INPX are: 1) need for lower dose of AZT for maintaining a therapeutic anti-retroviral level; 2) a longer interval period between AZT treatments; 3) a potential to enhance immunological response resulting from INPX treatment; 4) reduced costs of care for patients.

Topics: Acquired Immunodeficiency Syndrome; Drug Therapy, Combination; HIV; Humans; Inosine; Inosine Pranobex; Time Factors; Zidovudine

An unsuccessful treatment with recombinant alpha-2 interferon and isoprinosine in a patient with AIDS and Kaposi's sarcoma is reported.

Topics: Acquired Immunodeficiency Syndrome; Adult; Humans; Immunotherapy; Inosine; Inosine Pranobex; Interferon Type I; Male; Recombinant Proteins; Sarcoma, Kaposi

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

Applying flow cytometric analysis and a panel of monoclonal antibodies that define functional subsets and stages of lymphocyte differentiation, we found both inducer and suppressor regulating subsets of helper T cells to be depressed with concurrent increase in the functionally active effector suppressor T cells in prodromal homosexuals and patients with AIDS. Concomitantly a broad spectrum of aberrations in all stages of B cell developments were observed. Failure of isolated peripheral blood lymphocytes from these subjects to respond to formalin-fixed Staphylococcus aureus cowan 1 (SAC) indicated intrinsic defects in their resting B cells, while impairment in pokeweed mitogen (PWM)-induced blastogenesis coupled with increased levels of Ig secretion signified regulatory defects in their mature B cells, which may be related to helper-suppressor dysfunctions. Based on these findings, a multifactorial immunodysfunction in AIDS was proposed. The antiviral biological modulator drug isoprinosine was shown to enhance PWM-induced, T-cell dependent, B-cell blastogenesis and normalize the spontaneous secretion of Ig while showing no modulative effects on SAC-induced (resting B-cell) transformations. It also modified, in a selective fashion, the phenotypic coexpression of both HLA-DR and Leu8 antigen on helper and suppressor T cells. Among prodromal subjects at risk to develop AIDS, isoprinosine augmented the expression of both helper T-cell subsets while reducing the number of suppressor effector cells and activated suppressor cells. These interferences with the helper-suppressor regulatory loop may explain the therapeutic efficacy of this drug in the early stages of AIDS.

Topics: Acquired Immunodeficiency Syndrome; Homosexuality; Humans; Immunity, Cellular; Inosine; Inosine Pranobex; Male; Reference Values; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Topics: Acquired Immunodeficiency Syndrome; Hemophilia A; Humans; Immunization, Passive; Inosine; Inosine Pranobex; Interferon Type I; Lentinan; Lymphocyte Activation; Male; Neutrophils; Phagocytosis; Polysaccharides

Topics: Acquired Immunodeficiency Syndrome; Humans; Inosine; Inosine Pranobex

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

The in vitro effects of isoprinosine (ISO) on the production of IL-1 in AIDS patients and normal controls were investigated in this study. IL-1 production from adherent cells was measured by an indirect method using EL-4 cells. Five of eleven AIDS patients had depressed IL-1 production. Various concentrations of ISO were used to treat the adherent cells in vitro and the optimal concentration for stimulating IL-1 production was determined to be 100 micrograms/ml/10(6) cells. IL-1 production was augmented to normal or to near normal levels in four of five AIDS patients. Our results indicate that depressed immunity seen in some AIDS patients may be partly due to the depressed in IL-1 production and also that ISO can act as an immune potentiation in enhancing the production of this lymphokine in vitro.

Topics: Acquired Immunodeficiency Syndrome; Female; Humans; In Vitro Techniques; Inosine; Inosine Pranobex; Interleukin-1; Interleukin-2; Male; T-Lymphocytes

Functional and phenotypical parameters demonstrated significant aberrations in both prodromal males and patients with the acquired immune deficiency syndrome (AIDS). Impaired B-cell functions as quantitated by Staphylococcus aureas Cowan Strain I (SAC) and pokeweed mitogen (PWM)-induced blastogenesis, intracytoplasmic immunoglobulins and spontaneous immunoglobulin were associated with a significant decrease in Leu3+ cells but unrelated to Leu2+ lymphocytes. The functional subsets of the latter were further defined by monoclonal antibodies (Leu8 and HLA-DR) applying dual color flow cytometry. Activated and effector-suppressor subsets with the phenotypes Leu2+ HLA-DR+ and Leu2+ Leu8- were elevated while both subsets of helper and suppressor-inducing helper lymphocytes, Leu3+ Leu8- and Leu3+ Leu8+, were depressed. These data demonstrated a broad spectrum of dysfunction involving all 3 stages of B-cell development in AIDS as well as possible defects in the feedback suppressor loop which regulates both the helper and suppressor T-lymphocyte system and B-cell functions. While in vitro incubation with isoprinosine had no modulative effect on SAC-induced blastogenesis (resting B-cell activities), it did modulate both PHA, PWM-induced transformation and the spontaneous secretion of immunoglobulins (partially and fully activated B-cell activities). In co-incubation with PWM, isoprinosine augmented the expression of inducer cells for helper functions while enhancing to normal level the number of suppressor-inducing helper cells. In addition, it reduced activated and effector-suppressor cells to near normal range in the PBL of high risk homosexuals. Only marginal modulation, however, was observed in suppressor subsets of AIDS subjects. This interference with the defective feedback loop may account for the selective clinical and immunoregulatory actions of this drug.

Topics: Acquired Immunodeficiency Syndrome; Adjuvants, Immunologic; Adult; Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; B-Lymphocytes; Flow Cytometry; HLA-DR Antigens; Homosexuality; Humans; Inosine; Inosine Pranobex; Lymphocyte Activation; Male; Middle Aged; Phenotype; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Isoprinosine and Imuthiol are immunomodulators with a unique effect on T-cells. The possibility of using them in treating patients with acquired immunodeficiency syndrome related complex (ARC) was initially examined regarding their in vitro effects on peripheral blood mononuclear cells. In six ARC patients Isoprinosine (100 micrograms/ml) and Imuthiol (10 pg/ml) induced in vitro an early chromatin activation as measured by nuclear refringency test and potentiated phytohemagglutinin (5 micrograms/ml) in the same 20-min assay in the absence of fetal calf serum. In all patients an early phytohemagglutinin induced chromatin dispersion was observed with a dose related response before interleukin 2 production can occur. Isoprinosine and Imuthiol increased significantly both the percentage and the absolute number of T4+ cells when peripheral blood mononuclear cells were incubated for 4 days in RPMI supplemented with 10% fetal calf serum. No changes in T8+ cells were noted. Three homosexual ARC patients were then treated p.o. with Imuthiol (5-10 mg/kg/week) for 4 to 6 months. Without any deleterious effect a clinical improvement (in terms of adenopathy and opportunistic infection regression) and restoration of the response to recall antigens were observed in all three patients. One patient with less than 500 T4+ lymphocytes/mm3 exhibited a complete restoration of OKT profiles. In such patients clinical and immunological effects of Isoprinosine have already been reported by others. Altogether these preliminary results indicate that more data should be obtained on the effects of these two agents in ARC patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; Ditiocarb; Homosexuality; Humans; In Vitro Techniques; Inosine; Inosine Pranobex; Leukocyte Count; Lymphocyte Activation; Male; Phytohemagglutinins; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Thiocarbamates

Topics: Acquired Immunodeficiency Syndrome; Adult; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Homosexuality; Humans; Inosine; Inosine Pranobex; Lymphocyte Activation; Lymphocyte Cooperation; Lymphocytes; Male; Sarcoma, Kaposi; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Immunomodulative actions of isoprinosine were tested in 100 prodromal homosexual males and 23 patients who have been diagnosed with AIDS. All subjects showed reduced T helper cells although T suppressor cell counts were normal. Proliferative responses, particularly T cell-dependent B cell function, were severely impaired in prodromal and AIDS subjects. Upon co-cultivation of their lymphocytes with isoprinosine, significant upward modulation, and in some cases, normalization, of lymphocyte functions as monitored by PHA- and PWM-induced blastogenesis was achieved in prodromal subjects. Similar degrees of modulation but not normalization of lymphocyte functions were observed in patients with severe symptoms of AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adjuvants, Immunologic; Adult; Aged; Dose-Response Relationship, Immunologic; Homosexuality; Humans; Inosine; Inosine Pranobex; Leukocyte Count; Lymphocyte Activation; Male; Middle Aged; Phenotype; T-Lymphocytes

Topics: Acquired Immunodeficiency Syndrome; Bone Marrow Transplantation; Deltaretrovirus; Humans; Immunotherapy; Inosine Pranobex; Interferons; Interleukin-2; Levamisole; Lymphocyte Transfusion; T-Lymphocytes; Thymus Hormones; Vaccination

Topics: Acquired Immunodeficiency Syndrome; Antiviral Agents; Humans; Inosine; Inosine Pranobex; Virus Diseases

We report on a lethal course of an acquired immunodeficiency syndrome (AIDS) in a young female patient. She had spent her vacancies six years before diagnosis in Haiti, where a sexual intercourse with a Haitian man had occurred. Leading clinical symptoms consisted of recurrent Herpes simplex infections of the genital and perianal region as well as unexplained high temperatures. There were some typical laboratory and immunologic features of this disease with leukopenia, hypergammaglobulinemia, cutaneous anergy, a reduction of peripheral T-lymphocytes (OKT 3) and an almost complete loss of OKT 4 (helper cells) positive lymphocytes. The mitogenic response upon stimulation with allogeneic cells (MLC) or with the mitogens PHA, Con A and PWM was significantly reduced. There was no measurable interleukin-2 (IL-2) secretion of peripheral blood lymphocytes. Several immunostimulators (thymopentin, inosiplex, bestatin) were tested in lymphocyte proliferation assays in vitro. The mitogenic response could not be enhanced by neither of these substances. A clinical trial with Delimmun (inosiplex) for 14 days did not show any clinical or immunologic improvement in this patient. The intravenous application of high dose immunoglobulin G was without any observable effect. The proliferation inducing capacity of a highly purified IL-2 preparation on the AIDS cells in vitro led us to a clinical trial with this substance. We applied 100 Bödeker units of IL-2 per kg body weight and day subcutaneously for 16 days. A therapeutical effect, however, could not be observed. Cell marker analyses did not show significant changes in lymphocyte subpopulation composition under IL-2 therapy. There was an increase in the spontaneous cell proliferation 14 days after start of IL-2 therapy. The PHA- and IL-2 response of the AIDS cells, however, was unchanged. It cannot be excluded that an administration of IL-2 in earlier stages of AIDS may have beneficial effects.

Topics: Acquired Immunodeficiency Syndrome; Adjuvants, Immunologic; Adult; Antibody Formation; Female; Humans; Immunity, Cellular; Inosine Pranobex; Interleukin-2; Leucine; Leukocyte Count; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Peptide Fragments; Thymopentin; Thymopoietins

The in vitro effects of isoprinosine (ISO) on interleukin-2 (IL-2) production, the expression of Tac antigen (IL-2 receptor) on lymphocytes, and the ability of Leu 3(+) cells to absorb interleukin-1 (IL-1) were investigated in 10 patients with acquired immune deficiency syndrome (AIDS). In 9 of the 10 patients, production of IL-2 from mononuclear cells and Leu 3(+) cells was depressed; expression of Tac antigen on mononuclear cells and Leu 2(+) cells was found to be depressed in 9 of 10 patients. The ability of the Leu 3(+) lymphocytes to absorb IL-1 was depressed in all (four of four) patients studied. After ISO treatment, IL-2 production, Tac antigen expression and IL-1 absorption were restored to normal or near normal levels in most of the patients. These results suggest that ISO has an immunostimulating capacity in AIDS patients and that the potential of ISO in immune response restoration in AIDS patients deserves critical consideration.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antigens, Surface; Female; Humans; Inosine; Inosine Pranobex; Interleukin-1; Interleukin-2; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Male; Receptors, Immunologic; Receptors, Interleukin-2; Tumor Necrosis Factor Receptor Superfamily, Member 7

Topics: Acquired Immunodeficiency Syndrome; Drug Synergism; Drug Therapy, Combination; Humans; Immunotherapy; Inosine Pranobex; Interferon Type I; Interleukin-2; Male; Thymus Hormones

Topics: Acquired Immunodeficiency Syndrome; Antigens, Surface; Cells, Cultured; Humans; Inosine; Inosine Pranobex; Interleukin-2; Lymphocytes; Receptors, Immunologic; Receptors, Interleukin-2; Tumor Necrosis Factor Receptor Superfamily, Member 7

Topics: Acquired Immunodeficiency Syndrome; Concanavalin A; Diarrhea; Humans; Inosine; Inosine Pranobex; Lymphatic Diseases; Lymphocyte Activation; Phytohemagglutinins; Pokeweed Mitogens; T-Lymphocytes

Male prodromal homosexuals and patients with acquired immune deficiency syndrome (AIDS) exhibited similar immunological abnormalities but by different degrees. A reduction in the number of circulating T lymphocytes bearing the T-4 surface marker led to an altered ratio of Th to Ts subpopulations in both groups of subjects. Total numbers of suppressor cells (Ts) remained virtually similar in both study groups to that of the control subjects. Proliferative responses to T-cell mitogen (PHA) and T cell-dependent B-cell mitogen (PWM) were severely impaired in prodromal subjects and more so in the AIDS group. The response to PWM was unrelated to the total number of suppressor T cells but was associated with a significant decrease in helper T-cell number. The impaired lymphocyte functions of immunosuppressed subjects were potentiated by coincubation with isoprinosine in a selective fashion. While the percentage of upward modulation among homosexuals with normal lymphocyte functions was comparable to that obtained in control subjects, a higher degree of augmentation was achieved in AIDS patients and in prodromal subjects with impaired blastogenic responses. In none of the AIDS patients with severe immunodeficiencies, however, was the lymphocyte functions restored to the normal range established in the heterosexual controls. These results suggest the feasibility of eventual prophylactic utilization of isoprinosine in male homosexuals at high risk of developing AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; B-Lymphocytes; Homosexuality; Humans; In Vitro Techniques; Inosine; Inosine Pranobex; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Mitogens; T-Lymphocytes