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Interferon‐γ induced lethality in the late phase of Plasmodium vinckei malaria despite effective parasite clearance by chloroquine
Author(s) -
Kremsner Peter G.,
Neifer Stefan,
Chaves Mair F.,
Rudolph Roland,
Bienzle Ulrich
Publication year - 1992
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830221118
Subject(s) - chloroquine , parasitemia , biology , pentoxifylline , necrosis , immunology , interferon gamma , plasmodium falciparum , pharmacology , malaria , cytokine , genetics
Abstract A combination therapy was tested consisting of chloroquine and interferon‐γ (IFN‐γ) in the late phase of blood‐stage Plasmodium vinckei malaria in BALB/c mice. When mice were treated with three times 300 μg chloroquine at 24‐h intervals starting at a parasitemia of 30%‐50%, only 5 of 14 mice (36%) died 2–4 days after initiation of therapy. However, when infected mice received chloroquine plus 1 μg IFN‐γ at the same time, 14 of 18 mice (78%) died 0.5–3 days after start of therapy ( p < 0.05) despite clearance of parasitemia. The histopathology from mice dying after combination therapy revealed interstitial leukocyte infiltration of lung tissue, severe liver cell necrosis and kidney tubular necrosis. Pretreatment of P. vinckei ‐infected mice with pentoxifylline, a phosphodiesterase inhibitor, led to a significant decrease of IFN‐γ‐induced lethality ( p < 0.05). In contrast, pretreatment with neutralizing antibodies to tumor necrosis factor or with L‐N‐monomethyl arginine, the latter an inhibitor of the nitric oxide synthase, significantly increased lethality ( p < 0.05).