Melioidosis is a common cause of fatal community-acquired septicaemia and
pneumonia in endemic regions even with appropriate antibiotic treatments. The involvement
of inflammatory cytokines in the manifestation of melioidosis is well-documented. Antibacterial
and anti-inflammatory therapies may prove more efficacious against melioidosis
rather than just anti-bacterial therapy alone. The phosphatidylinositol 3-kinase (PI3K)/Akt
pathway has a central role in regulating the host inflammatory response; and glycogen
synthase kinase-3β (GSK3β), a downstream effector molecule within this axis, plays a pivotal
role in regulating the production of pro- and anti-inflammatory cytokines. The anti-malarial
drug, chloroquine is a novel activator of Akt, and can elicit inhibition of GSK3β via PI3K/Akt
signalling. LiCl, a GSK3 inhibitor is reported to increase survivability and modulate cytokine
production in B. pseudomallei-infected mice. Here we determined the effects of chloroquine
administration on animal survivability, cytokine levels and phosphorylation states of GSK3β
(Ser9), Akt (Ser473) and NF-κB p65 (Ser536) in a murine model of acute melioidosis infection.
Administration of 50 mg/kg b w chloroquine improved survivability (mean 67.0 ± 6.3%) of
mice infected with 3 X LD50 B. pseudomallei compared to controls. Bacterial loads in spleen,
liver, lung and blood of infected mice administered with chloroquine were significantly lower
than controls. Western blot analysis revealed that the intensities of pAkt (Ser473) and pGSK3β
(Ser9) in liver samples of mice administered with chloroquine were significantly (P