Effect Of Isoprinosine Research Articles

Effect of isoprinosine on 3'-Azido-3'-deoxythymidine uptake and phosphorylation in human peripheral blood mononuclear cells.

The effect of the immunomodulating agent Isoprinosine on AZT uptake and phosphorylation in human blood monocytes/macrophages was examined. AZT (1-15 microM) uptake in monocytes/macrophages was rapid and dose- and time-dependent. The main metabolite formed after 1 h was AZT-5'-monophosphate. Isoprinosine cotreatment (5-50 microM) had no significant effect on AZT (5 microM) uptake. On the other hand, Isoprinosine increased the formation of AZT-diphosphate metabolites and, more intensively, of AZT-triphosphate (AZT-TP) metabolites after 1 h incubation. Extended exposure (4 h) resulted in complete absence of AZT-TP due to dephosphorylation of these metabolites or blocking of AZT phosphorylation.

The effect of isoprinosine and levamisole on factors relevant to protection of calves against respiratory disease

Experiments to characterize the effects of two immunomodulators, namely, isoprinosine and levamisole, on factors relevant to the resistance of calves to respiratory infection were undertaken. Daily oral doses of isoprinosine decreased the influx of neutrophils into the respiratory tract, increased membrane immunoglobulin and complement receptor expression on cells from bronchoalveolar lavage samples and decreased the severity of respiratory disease. Additional intravenous doses produced similar effects on neutrophil migration to the respiratory tract and on membrane receptor expression, but the changes were no greater than those seen with oral isoprinosine alone. No significant changes in the anti-bacterial activity of cells in bronchoalveolar lavage samples followed isoprinosine treatment. In vitro incubation of pulmonary alveolar macrophages harvested from normal calves with isoprinosine increased their expression of immunoglobulin and complement receptors. Levamisole did not affect neutrophil migration to the lower respiratory tract or membrane receptor expression by pulmonary alveolar macrophages after in vivo or in vitro treatment. The immunomodulatory effects of isoprinosine beneficially increase the resistance of calves to respiratory disease, and are potentially useful in the control of infectious diseases of farm animals.

Effect of isoprinosine on IL-2, IFN-γ and IL-4 production in vivo and in vitro

The effects of an immunopotentiating drug, isoprinosine, on the splenocytes of BALB/c mice to produce cytokines were investigated. Isoprinosine enhanced IL-2 production, upregulating the expression of IL-2 receptor in vitro. It also significantly increased the IFN-γ secretion and decreased the IL-4 production in vivo. The significance of these findings in terms of immune regulation is discussed.

No effect of isoprinosine of HIV infection in vitro

No effect of isoprinosine of HIV infection in vitro

Effect of Isoprinosine on Lymphocyte Proliferation and Natural Killer Cell Activity Following Thermal Injury

The effect of in vivo administration of Isoprinosine (ISO) on, i) the proliferation of splenic lymphocytes in response to the T-cell mitogen, concanavalin-A (Con-A) and, ii) the natural killer (NK) cell cytotoxicity was studied following a full skin thickness burn injury in a rat model. Administration of ISO (100 mg/kg body wt/day) twice daily, resulted in significant augmentation of the proliferative responses of lymphocytes compared to non-treated burned animals, at 7 days post injury. However, it did not effect the lymphoproliferation at 14 days post injury, the time period at which a complete suppression of lymphocyte proliferation was observed in burned non-treated animals. Also, the proliferation of lymphocytes from normal nonburned animals was not affected by treatment with ISO. ISO treatment of the burned animals resulted in a significant increase in the NK cytotoxicity compared to non-treated burned animals. As with Con-A responses, ISO administered to control nonburned animals did not have any effect on NK cell cytotoxicity. Our studies thus indicate that ISO can be a potential immunomodulator of suppressed immune function following thermal injury, particularly in patients whose lymphocyte responses to T cell mitogen Con-A are not completely suppressed.

Immunomodulatory effect of isoprinosine and levamisole in chronic active HBV-positive hepatitis

Immunomodulatory effect of isoprinosine and levamisole in chronic active HBV-positive hepatitis

Isoprinosine restores in vitro T lymphocyte functions of cyclophosphamide immunosuppressed mice

The effect and the mechanism of action of isoprinosine has been investigated in several models of in vitro activation of lymphocytes. Isoprinosine added to spleen cell cultures enhanced lymphocyte proliferation induced by concanavalin A or allogeneic stimulation as well as the generation of allospecific cytotoxic T cells. The effect of isoprinosine on T lymphocyte proliferation in vitro was specially marked when mice were treated with cyclophosphamide (75–200 mg/kg) 16–24 h before the onset of cultures. No effect was observed on B cell proliferation to LPS. Addition of inosine or adenosine also enhanced proliferation of cells from both normal and cyclophosphamide treated mice. Isoprinosine and inosine and, more markedly, adenosine, augmented interleukin-2 activity in concanavalin A supernatants of spleen cells from the same animals.

Effect of isoprinosine on sialylation of interleukin-2

The effects of Isoprinosine (ISO) on interleukin-2 (IL-2) production by human peripheral blood mononuclear cells (PBMC) were investigated. Treatment (of human PBMC) with ISO enhanced IL-2 production by PBMC from 7 of 10 normal individuals. However, no augmentation of IL-2 production was observed when cultures of HUT-78 cells, a human leukemic T cell line, were treated with ISO. IL-2 purified from supernatants of human PBMC treated with ISO exhibited p I values of 5.5 and 6.4. IL-2 prepared from untreated PBMC exhibited a single p I value of 8.2. The p I value of IL-2 prepared from ISO-treated PBMC shifted to 8.2 after treatment with neuraminidase, demonstrating that the IL-2 molecules isolated from ISO-treated PBMC possessed sialic acid. The p I values of the IL-2 isolated from ISO-treated and untreated HUT-78 culture supernatants were identical (p I = 7.8) and were not modified by neuraminidase treatment. These results suggest that the increase in IL-2 production following treatment of PBMC with ISO may be mediated through the activation of a distinct subset of IL-2 producing cells. Furthermore, the sialylation of IL-2 may be of physiologic and immunopharmacologic importance.

Differential effect of isoprinosine on lymphocyte proliferation: Comparison of two tissue culture media

Isoprinosine (ISP) has been reported to stimulate a variety of immunological responses. This study showed a differential effect of this drug on the proliferative response of human peripheral blood mononuclear cells to phytohemagglutinin (PHA). ISP was found to increase this proliferative response when Eagle's Minimum Essential Medium (MEM) was used. When Medium-199 (M-199) was used to culture the cells, no increase in the proliferative response was observed. This inhibition by M-199 of the ISP effect on PHA-stimulated cells has been traced to the presence of the purines adenine and hypoxanthine in M-199.

Effect of isoprinosine on interleukin 1 and 2 production and on suppressor cell activity in pokeweed mitogen stimulated cultures of B and T cells

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.

Modulatory effect of isoprinosine on lymphocyte proliferative response under immunodepressive conditions.

In the present work the effect of Isoprinosine on the mitogenic responses of T and B lymphocytes has been studied. We have found that Isoprinosine can enhance in vitro the response to Concanavalin A. This enhancement was more apparent in cell cultures showing an initially low blastogenic response. In low responses artificially induced by treatments in vivo with cyclophosphamide, our results indicate that Isoprinosine, administered in vivo, does not enhance the response to Con A of treated mice. However, addition of Isoprinosine (75 micrograms/ml) to cultures of spleen cells from mice previously treated with cyclophosphamide enhanced the suppressed response up to normal levels. Neither in vivo nor in vitro Isoprinosine treatments increased the response of lymphocytes to lipopolysaccharide, but usually inhibited the blastogenesis of B cells.

The Effect of Isoprinosine on the Pha Response of Monocyte-Depleteo and Undepleted Periphesal Blood Mononuclear Cells

Isoprinosine has been reported to stimulate immunological responses involving different cell types. This study attempted to identify which cell type responds to isoprinosine in the blast transformation assay using the mitogen phytohemagglutinin (PHA). Human peripheral blood mononuclear cells, and the same cell population depleted of monocytes, were used to determine whether the absence of monocytes alters the response to isoprinosine. To determine whether there is a critical period of time during the assay when isoprinosine has its effect, the cells were selectively preexposed to drug and/or mitogen for a limited period of time, then cultured. Depletion of monocytes in itself augmented the response to mitogen, but the response could still be potentiated by isoprinosine, indicating that the drug's effect was on cells other than monocytes. Preexposure to isoprinosine and/or PHA, followed by culture with PHA with or without isoprinosine, showed that PHA initiates transformation within the first 3 hours and that initiation, a monocyte function, is not sensitive to isoprinosine. Both approaches suggest that isoprinosine does not affect monocytes and that it probably acts on T cells to produce its stimulatory effect in this in vitro assay.

In vitro effect of isoprinosine and an analogue(NPT 15392) on murine T cell differentiation and function

In vitro effect of isoprinosine and an analogue(NPT 15392) on murine T cell differentiation and function

Effect of Isoprinosine Against Challenge with A(H 3 N 2 )/Hong Kong Influenza Virus in Volunteers

Volunteers were challenged with A(H(3)N(2))/Hong Kong/8/68 influenza virus while being given prophylaxis with either isoprinosine or placebo in a double-blind experiment. Isoprinosine, which had demonstrable antiviral activity in animal models, did not appear to protect humans from clinical influenza. The only beneficial effect of the drug observed was a slight, but significant, reduction in virus shedding.