The immunomodulatory action of inosiplex in relation to its effects in experimental viral infections

The effect of inosiplex (Isoprinosine) on viral replication, experimental viral infections and host immune functions has been examined. Inosiplex was found to have a broad spectrum of antiviral activity, inhibiting the RNA viruses, influenza (INFV) and parainfluenza (PIV), as well as the DNA viruses, herpes simplex (HSV) and vaccinia (VACV). However, the antiviral effects were modest when compared to amantadine and adenine arabinoside (ARA-A). Inosiplex in vivo caused a statistically significant increase in survival of treated animals (hamster, mice) infected with RNA or DNA viruses. This effect of inosiplex was apparent in animals which were previously immunosuppressed. Inosiplex, at optimal dose, conferred total protection in treated mice against secondary influenza infection. Since this was accompanied by statistically significant increases in serum anti-hemagglutinin and anti-neuraminidase titers, an effect of inosiplex on host defenses against secondary viral infection was implicated. This effect was further demonstrated by passive transfer of protection by splenocytes from inosiplex-treated donors to untreated recipients. Inosiplex was found to enhance the mitogen- (PHA-, ConA and MLC-) induced blastogenesis of lymphocytes from untreated mice. The LPS response was not affected. Inosiplex added in vitro caused a dose-dependent increase in the primary immune anti-SRBC response in vitro, as determined by direct and indirect PFC; there was also a dose-dependent effect on the secondary in vitro direct and indirect PFC responses. Inosiplex in vivo enhanced the primary immune response to SRBC, as determined by direct PFC assay; this was also the case for immunosuppressed mice. The drug enhanced delayed type hypersensitivity to picryl chloride in the mouse. Macrophage function was also enhanced by inosiplex, as was apparent from phagocytosis of SRBC. Gamma interferon production from murine lymphocytes was augmented by inosiplex in vitro. Treatment with inosiplex had no effect on natural killer cells or on antibody dependent cellular cytotoxicity. Thus, the pronounced effect of inosiplex on secondary viral infections may result through two different mechanisms: a direct antiviral effect and an elevation of multiple parameters of host immunity, which are usually compromised during viral infection. The latter mechanism may be the more important.