An in vitro study on the effects of isoprinosine on immune responses in cancer patients
Tsang KY, Fudenberg HH, Pan JF, Gnagy MJ, Bristow CB. Int J Immunopharmacol 1983;5(6):481-90.
The in vitro effects of Isoprinosine on the immune responses of cancer patients were investigated. Forty seven patients with primary tumors (26 lung carcinoma, 14 breast adenocarcinoma, 7 melanoma) were studied. Concanavalin A (ConA)-induced lymphocyte proliferation, natural killer cell (NK) activity, and monocyte chemotaxis were measured. In 40 of the 47 patients (85%), ConA-induced lymphocyte proliferation was depressed; NK activity was depressed in 32 (68%), and monocyte chemotaxis was found to be depressed in 36 (77%). In the presence of Isoprinosine, all three parameters were restored to normal or near normal levels in those that were depressed.
Number of helper T cells and phytohemagglutinin stimulation correlate in cancer patients
Richner J, Ambinder EP, Hoffmann K, Feuer EJ, Bekesi G. Cancer Immunol Immunother 1991;34(2):138-42.
Mononuclear cells from 12 normal controls (co), 10 advanced untreated (c1), and 6 advanced treated cancer patients (c2) have been isolated. The numbers of mononuclear cells bearing Leu1, Leu2, Leu3, Leu2/HLA-DR and LeuM3 were measured with a fluorescence-activated cell sorter. Only the quantity of helper T cells (Leu3) was decreased in cancer patients (co: 0.89, cl: 0.32, c2: 0.44 x 10(9)/l). The addition of indomethacin or isoprinosine to phytohemagglutinin-culture assay increased the proliferation of lymphocytes from both the cancer patients and normal controls.
Therapy of secondary T-cell immunodeficiencies with biologicalsubstances and drugs
Hadden JW, Hadden EM. Med Oncol Tumor Pharmacother 1989;6(1):11-7.
Thymus-dependent (T) lymphocyte defects are common in cancer. Interleukins (IL), particularly IL-1 and IL-2, appear to be complementary to the actions of thymic hormones in promoting T-cell development. Two classes of thymomimetic drugs have been identified and are represented by levamisole and Isoprinosine. These drugs mimic by indirect and direct actions, respectively, the actions of thymic hormones. These agents may now be more effectively integrated with cytodestructive therapy in cancer treatment.
Hadden JW. Int J Immunopharmacol 1994 Sep;16(9):703-10
The author concludes that "thymomimetic" peptides like thymosin alpha 1 or drugs like levamisole or Isoprinosine alone or in conjunction with interleukins may augment TH-1 and DTH responses. These approaches are seeing increasing emphasis in new treatment strategies for cancer and infections like HIV.
Results of the treatment of papilloma and bronchogenic carcinoma with interferon alpha
Szklarz E et al. Pol Tyg Lek 1990 Aug 6-13;45(32-33):669-72 (Article in Polish).
The results of treatment of two patients with bronchial tumor and papillomatosis with interferon alpha combined with cytostatics and Isoprinosine were compared. Interferon alpha was administered to the bronchi and directly into the tumors. Complete recovery was achieved in case of the bronchial papillomatosis and partial remission in case of cancer. It seems that combined interferon, cytostatic and Isoprinosine therapy may prolong patients' survival.
Potentiation of cytotoxic effects of 5-fluorouracil by inosiplex on cancer cells
Miyoshi T, Ogawa S, Nobuhara M, Namba M. Gan To Kagaku Ryoho 1984 Mar;11(3):440-4
Effects of inosiplex on the potentiation of cytotoxicity of 5-FU were investigated in vitro and in vivo. In vitro studies demonstrated that cytotoxic effects of 5-FU on cloning efficiency of HeLa cells were prominently enhanced by inosiplex, while inosiplex alone showed no cytotoxicity at the concentrations examined. Further, the survival time of mice intraperitoneally inoculated with Ehrlich ascites tumor cells was investigated. The mean survival time of mice treated with the combination of 5-FU and inosiplex significantly prolonged as compared with that of control animals or mice treated with inosiplex alone or 5-FU alone. The present results indicate that a combined administration of 5-FU and inosiplex may be effective in the treatment of human cancers.
Oral proliferative verrucous leukoplakia (PVL); open trial of surgery compared with combined therapy using surgery and methisoprinol in papillomavirus-related PVL
Femiano F, Gombos F, Scully C. Int J Oral Maxillofac Surg 2001 Aug;30(4):318-22
In an open trial of 25 patients with oral HPV-positive PVL, a combined therapy using surgery and methisoprinol (Isoprinosine) was compared with surgery alone. Overall, by 18 months follow-up, there were 18 recurrences in the group treated by surgery alone, compared with four in those also receiving methisoprinol. The use of this antiviral agent appeared to offer a significant enhancement to the surgical management of PVL.
Combined therapy with Isoprinosine and CO2 laser microsurgery for the treatment of laryngeal papillomatosis
Elo J, Mate Z. Arch Otorhinolaryngol 1988;244(6):342-5.
Laser surgery is the current method of choice for treating laryngeal papillomatosis, but it has not solved completely the problems of recurrences. To make treatment more effective, a therapeutic regimen that combines laser microsurgery with the immunostimulant methisoprinol (Isoprinosine) was developed. Observations in 18 patients have shown that this combined management was more successful than using a single modality with either the laser or Isoprinosine alone. The combined approach was also effective in recurrent cases, with the timing of the combination influencing the results of the treatment given.
Efficacy of inosine pranobex oral therapy in subclinical human papillomavirus infection of the vulva: a randomised double-blinded placebo controlled study
Tay SK. Int J STD AIDS 1996 Jul;7(4):276-80
A randomized double-blind placebo controlled study with 46 patients was carried out to assess the efficacy of Isoprinosine (1 g orally 3 times a day for 6 weeks) in the treatment of symptomatic subclinical human papillomavirus infection of the vulva. A total of 14 (63.5%) of the Isoprinosine treated patients and 4 (16.7%) of the placebo treated patients showed significant vulval epithelial morphological improvement (P = 0.005) at 2 months after initiation of treatment. It is concluded that Isoprinosine demonstrated a significant pharmacological activity in subclinical HPV infection of the vulva and should be considered an alternative treatment for the condition.
Immunological effects of isoprinosine as a pulse immunotherapy in melanoma and ARC patients
Pompidou A, Soubrane C, Cour V, Telvi L, Meunier C, Jacquillat C. Cancer Detect Prev Suppl 1987;1:457-62.
Immunomodulatory effects 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. 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.
Imunovir in the treatment of immunodepression of diverse etiology
O'Neill BB, Glasky AJ. Cancer Detect Prev Suppl 1987;1:329-31
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).
Clinical Improvement In Chronic Fatigue Syndrome Is Associated With Enhanced Natural Killer Cell Mediated Cytotoxicity: The Results Of A Pilot Study With Isoprinosine®
1A. Kumar, 2E. Turgonyi, 3B. Hyde, 1C. Galvis, 1W. Lim and 1F. Diaz-Mitoma
1Departments of Pediatrics, Division of Virology, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa; 2Newport Pharmaceuticals Ltd., Ireland; and 3Nightingale Research Foundation, Ottawa, Ontario, Canada.
Chronic fatigue syndrome (CFS) is associated with several immune abnormalities, such as decreased natural killer (NK) cell mediated cytotoxicity and dysregulated production of cytokines. The clinical impact of Isoprinosineâ (immunomodulator / antiviral) on various immune functions in a total of 16 CFS patients diagnosed according to the CDC CFS definition was evaluated. Patients were followed for 28 weeks. Clinical improvement based on the clinical staging was observed in 6 out of 10 patients (60%). CFS patients at baseline compared to normal controls exhibited a significantly decreased NK activity as well as decreased mitogen-induced production of IL-10, IL-12 and IFN-g in PBMC. The clinically improved patients showed a significantly enhanced NK activity [LU (5 and 15%)/106] which correlated with the duration of the treatment (p< 0.03). A significant increase in IL-12 production by T cell mitogen stimulated PBMC was observed in clinically improved patients treated for 28 weeks compared to the patients on placebo (p < 0.02). Treatment with Isoprinosineâ for 12 weeks did not appreciably influence the production of IL-1a and IL-10. However, discontinuation of treatment resulted in enhanced production of both IL-1a and IL-10 only in clinically improved patients. When treatment was started again at week 16, significantly decreased production of these two cytokines was observed. Treatment with Isoprinosineâ for prolonged periods (28 weeks) also resulted in the enhanced number of CD4+ T helper cells and CD4+, HLA-DR+ T cell number in peripheral blood only in clinically improved patients. These results suggest the clinical efficacy of Isoprinosineâ and its potential to enhance NK cell activity. In view of the small number of patients, further studies are required to investigate the contribution of Isoprinosineâ-mediated immune effects to the pathogenesis of CFS.
The paper was presented at The American Association of Immunologists and the Clinical Immunology Society Joint Annual Meeting, "Immunology 2000" May 12-16, 2000 Washington State Convention and Trade Center, Seattle, Washington.