Effects of interferon in malaria infection
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R K Maheshwari1, V Srikantan, D Bhartiya
1Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD.
Abstract:
Earlier, we reported that prophylactic treatment with human interferon gamma (rHuIFN-gamma) protected monkeys against Plasmodium cynomolgi B malaria infection. We have tested the efficacy of rHuIFN-gamma on relapsing stage of experimental P. cynomolgi B malaria infection in rhesus monkeys. No effect of rHuIFN-gamma was seen against experimental relapsing stage compared with controls; however, it appears that chloroquine (CHL) may have interfered with the antimalarial effect of IFN, since treatment with CHL inhibits the antiviral activity of mouse alpha/beta IFN and polyinosinic-polycytidylic acid (poly I:C) against Semliki forest virus (SFV) in mice. These results may have clinical implications especially with the use of IFN against virus infection, cancer and in parasitic infections in malaria endemic areas where CHL is one of the most widely used antimalarial drugs. Our result also shows that CHL treatment enhances the virus replication in mice and suggest a possible connection between AIDS and malaria infection, since the spread of AIDS has been rapid in parts of tropical Africa that have a high incidence of malaria, and chloroquine has been frequently used in the chemotherapy of malaria.
Insights
Human interferon gamma (IFN) did not prevent malaria relapse in monkeys. Chloroquine (CHL) may interfere with IFN
Area of Science:
- Immunology
- Infectious Diseases
- Pharmacology
Background:
- Previous studies demonstrated prophylactic efficacy of recombinant human interferon gamma (rHuIFN-gamma) against Plasmodium cynomolgi B malaria in monkeys.
- The efficacy of rHuIFN-gamma during the relapsing stage of malaria warrants investigation due to potential drug interactions.
Purpose of the Study:
- To evaluate the efficacy of rHuIFN-gamma in the relapsing stage of experimental Plasmodium cynomolgi B malaria in rhesus monkeys.
- To investigate potential interference of chloroquine (CHL) with interferon (IFN) therapy.
Main Methods:
- Rhesus monkeys with relapsing Plasmodium cynomolgi B malaria were treated with rHuIFN-gamma.
- Control groups received no treatment or other interventions.
- Antiviral activity assays were performed in mice treated with CHL and exposed to Semliki Forest Virus (SFV) with or without IFN or polyinosinic-polycytidylic acid (poly I:C).
Main Results:
- rHuIFN-gamma showed no significant effect on the relapsing stage of P. cynomolgi B malaria in rhesus monkeys compared to controls.
- Chloroquine treatment appeared to interfere with the antimalarial effect of IFN.
- Chloroquine treatment enhanced virus replication in mice, suggesting potential interactions with IFN-based therapies.
Conclusions:
- Interferon gamma is not effective against the relapsing stage of experimental malaria in monkeys.
- Chloroquine may antagonize the therapeutic effects of interferons, with potential clinical implications for treating viral, cancer, and parasitic infections in malaria-endemic regions.
- The observed enhancement of viral replication by chloroquine suggests a possible link between malaria, chloroquine use, and increased susceptibility to viral infections like AIDS.