NDLI: Therapy with a Combination of Low Doses of Interleukin 12 and Chloroquine Completely Cures Blood-Stage Malaria, Prevents Severe Anemia, and Induces Immunity to Reinfection

Content Provider	PubMed Central
Author	Mohan, Karkada Sam, Hakeem Stevenson, Mary M.
Editor	Mansfield, J. M.
Copyright Year	1999
Abstract	The immunoregulatory cytokine interleukin 12 (IL-12) induces host resistance against experimental malaria. In this study, we tested the feasibility of using IL-12 in combination with chloroquine (CQ) to rescue susceptible A/J mice from lethal blood-stage Plasmodium chabaudi AS infection. Combined treatment with low doses of CQ and IL-12 resulted in a >15-fold reduction in the parasite load and 100% survival of A/J mice with established infections. Compared to control mice, which succumbed to severe anemia, CQ-plus-IL-12-treated mice had significantly higher early- and late-stage erythroid-cell progenitors in the bone marrow and spleen, resulting in significantly higher hematocrits, erythrocyte counts, and percentages of reticulocytes. Production of parasite-specific gamma interferon (IFN-γ) by splenocytes from these mice was upregulated >20-fold relative to controls in parallel with enhanced IFN-γ mRNA expression. Further, enhanced responsiveness to IL-12 and increased downstream IFN-γ production in CQ-plus-IL-12-treated mice was evident from increased mRNA expression for the β1 and β2 subunits of IL-12 receptor in the splenocytes. Moreover, this combined therapy induced higher levels of anti-malaria antibodies than did CQ alone as well as sterile immunity against reinfection. Because IL-12 can be used at low doses and is effective even in established infections, it may be feasible to use this immunochemotherapeutic approach in human malaria.
Starting Page	513
File Format	PDF
ISSN	10985522
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	2
Volume Number	67
Language	English
Publisher	American Society for Microbiology
Publisher Date	1999-02-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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