Publication: POSSIBLE INVOLVEMENT OF IFN-γ IN EARLY MORTALITY OF PLASMODIUM BERGHEI NK65-INFECTED BALB/ C MICE AFTER FEBRIFUGINE TREATMENT
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2008-12
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S OUTHEAST A SIAN J T ROP M ED P UBLIC H EALTH
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Abstract
Parasitemia patterns, survival and cytokine levels of Plasmodium berghei NK65-in-
fected BALB/c mice, treated orally with the alkaloidal mixture of febrifugine and isofebrifugine
at a dose of 1 mg/kg twice a day for 4 consecutive days were monitored. Whereas the un-
treated mice showed a progressive increase in parasitemia and ultimate death, the alkaloid
mixture-treated group showed a transient suppression of parasitemia during the course of
treatment. However, the parasitemia increased on discontinuation of treatment, leading to earlier
death of mice in the treated group than in the infected but untreated controls. Mice in the
infected but untreated group displayed a significant elevation in serum IFN-γ levels during the
first week post-infection (pI) and from Day 14 pI, relative to the levels in the uninfected con-
trols. In contrast, although mice in the alkaloid mixture-treated group displayed no significant
elevation in serum IFN-γ levels during the first week pI, they showed considerable levels on
Day 14 pI. There were no significant differences in serum IL-4 levels among the groups. The
titers of the parasite-specific IgG1, IgG2a, IgG2b and IgG3 were significantly elevated from
Day 11 pI in both the treated and untreated groups. There was a significant difference in sur-
vival duration between the IFN-γ-/- mutant and BALB/c mice. IFN-γ-/- mutant mice showed a
decrease in parasitemia levels while receiving medication, which was significantly lower than
those of the treated BALB/c mice. The results of the present study suggest that although
IFN-γ is significant for protective immunity in mice with malaria infection, it may play an adverse
role post-medication, causing earlier mortality of treated BALB/c mice