Potentiation by levamisole, methisoprinol, and adenine or adenosine of the inhibitory activity of human interferon against encephalomyocarditis virus

Abstract

The antiviral action of different human interferons against encephalomyocarditis virus in HeLa cell cultures was analyzed. Cell treatment with levamisole (200 ,ug/ml), methisoprinol (1 mg/ml), or adenine or adenosine (33 or 100 ,g/ml, respectively) potentiated the anti-encephalomyocarditis virus activity of human interferon by 8-to 32-fold. A higher level of potentiation (256-fold) was achieved either by combined treatments with levamisole plus methisoprinol or by treatment with one of these compounds plus adenine or adenosine.Interferons (IFNs) are a group of proteins which influence diverse biological activities, including the inhibition of the replication of many viruses. Among these influences, the blockade of encephalomyocarditis (EMC) virus has been widely documented (3, 9, 12-15, 17, 19 (1,8,10,18).Levamisole is an antihelmintic drug of veterinary use, the capability of which to restore depressed immune responsiveness has led to its clinical challenge (16). The biochemical mode of action of levamisole is still unknown. It has been proposed that levamisole alters the intracellular cyclic nucleotide concentration by increasing the cGMP/cAMP ratio (7). Methisoprinol (isoprinosine, inosiplex) has been considered to be an antiviral agent. However, it has no direct antiviral effect (5). Rather, methisoprinol seems to act by enhancing the host immune response to viral infection. According to this proposal, a stimulatory effect of methisoprinol on both the antiviral (EMC virus) and antitumor actions of IFN has been reported in animals (4,6,11 For quantitation of virus yields, samples (0.5 ml each) of infected cultures were added to L929 cell monolayers (60-mm-diameter petri dishes). After 60 min of infection, nonadsorbed virus was removed, and the monolayers were overlaid with 6 ml of growth medium supplemented with 3% calf serum and 0.7% purified agar (Oxoid Ltd., London, England) and were further incubated at 37°C. PFUs were counted 3 h after staining with 0.08% neutral red 3 days after incubation.When HeLa cell cultures were pretreated with different concentrations of alpha or gamma IFNs and infected with 192

Levamisole Treatment Enhances Protective Antibody Response to Hepatitis B Vaccination in Hemodialysis Patients

“…Kimball and his associates (26) showed also that oral administration of levamisole to mice results in a twofold increase of IL‐1 production by their peritoneal macrophages stimulated in the presence of lipopolysaccaride. The possibility of biologic modulation is also supported by the finding that levamisole potentiates the activity of human interferon and IL‐2 (27,28).…”

Leukoencephalopathy induced by levamisole alone for the treatment of recurrent aphthous ulcers

“…5 Levamisole increases serum levels of interleukin-2 receptor in patients with cancer 6 and potentiates the production interferon and interleukin-2 in humans. 7,8 In normal mice, levamisole is not directly toxic to myelin. However, when administered to mice infected with a demyelination-inducing virus (Theiler's virus), demyelination and inflammation are augmented and accelerated.…”

Meta‐analysis: levamisole improves the immune response to hepatitis B vaccine in dialysis patients

“…It has been reported that levamisole stimulates T cells or macrophages; in addition, it restores delayed hypersensitive reactions in immune‐depressed patients 34 . Recent studies have reported that levamisole increases serum levels of IL‐2 receptors in patients with cancer 35 and IL‐1 production in mice models 36 . Levamisole is metabolized by the liver and then secreted from the kidney; no clearance by haemodialysis or peritoneal dialysis has been demonstrated.…”