Mechanism of Action of Isoprinosine
Isoprinosine (inosine pranobex) exerts dual immunomodulatory and antiviral effects through enhancement of T-cell proliferation, augmentation of natural killer cell activity, induction of pro-inflammatory cytokines (particularly TNF-α and IFN-γ), and direct inhibition of viral RNA synthesis. 1
Immunomodulatory Mechanisms
T-Cell Enhancement and Cytokine Induction
Isoprinosine significantly enhances TNF-α secretion in both short-term (24-hour) and prolonged (72-hour) lymphocyte cultures, while also increasing IFN-γ production in extended cultures. 2
The drug induces rapid proliferation of T-cell subsets and restores deficient immune responses in immunosuppressed patients through enhancement of T-cell lymphocyte proliferation and activity. 1
In healthy adults, isoprinosine increases serum levels of IFN-γ, IL-2, IL-10, and TNF-α, with peak elevations occurring at 7-10 days after treatment initiation. 3
IL-2 levels demonstrate a biphasic response, with initial elevation followed by a return to baseline, then a second rise at day 42 after treatment. 3
Regulatory Effects on Anti-Inflammatory Pathways
Isoprinosine suppresses IL-10 production by PHA-stimulated lymphocytes in a dose-dependent manner in both 24-hour and 72-hour cultures, which is particularly relevant as IL-10 is an anti-inflammatory cytokine that can dampen immune responses. 2
IL-10 levels remain elevated from day 7 to day 28 of measurement in treated individuals, suggesting sustained modulation of regulatory immune pathways. 3
Antiviral Mechanisms
Direct Viral Inhibition
Isoprinosine affects viral RNA levels and inhibits growth of multiple viruses through mechanisms that remain incompletely understood but involve interference with viral replication machinery. 1
The drug demonstrates particularly strong antiviral activity against adenoviruses (HAdV-2 and HAdV-5) and human parainfluenza virus type 2 (HPIV-2), with weaker effects against enteroviruses and HPIV-4. 4
Higher concentrations of isoprinosine (400-800 µg/mL) strongly inhibit viral multiplication across multiple virus families, though increasing concentrations beyond 400 µg/mL provide only marginal additional benefit. 4
Cellular Safety Profile
- Isoprinosine shows no cytotoxic activity on human cell lines (A549) at therapeutic concentrations (50-800 µg/mL), with cell viability maintained at approximately 98.36%. 4
Clinical Correlation with Cytokine Patterns
A moderate negative correlation exists between IFN-γ and other measured cytokines (IL-2, IL-10, TNF-α), with Spearman's correlation coefficients of approximately -0.63, suggesting complex regulatory feedback mechanisms. 3
The pleiotropic immunomodulatory effects result in restoration of immune function in patients with weakened immunity, making the drug particularly applicable for viral infections in immunocompromised states. 2
Proposed Mechanisms Requiring Further Investigation
The exact biochemical pathways through which isoprinosine modulates intracellular processes remain unclear despite nearly five decades of clinical use since 1971. 1
The drug's ability to induce pro-inflammatory cytokines that play crucial roles in immune resistance against various pathogens suggests potential applications beyond currently approved viral indications, including possible use as adjunct therapy in conditions like tuberculosis. 5