The CXC chemokines gamma interferon (IFN-gamma)-inducible protein 10 and monokine induced by IFN-gamma are released during severe melioidosis

Gamma interferon (IFN-gamma)-inducible protein 10 (IP-10) and monokine indu ced by IFN-gamma (Mig) are related CXC chemokines which bind to the CXCR3 r eceptor and specifically target activated T lymphocytes and natural killer (NK) cells. The production of IP-10 and Mig by various cell types in vitro is strongly dependent on IFN-gamma. To determine whether IP-10 and Mig are released during bacterial infection in humans, we measured plasma levels of IP-10 and Mig in patients with melioidosis, a severe gram-negative infecti on caused by Burkholderia pseudomallei. IP-10 and Mig were markedly elevate d in patients with melioidosis on admission, particularly in blood culture- positive patients, and remained elevated during the 72-h study period. Leve ls of IP-10 and Mig showed a positive correlation with IFN-gamma concentrat ions and also correlated with clinical outcome. In whole blood stimulated w ith heat-killed B. pseudomallei, neutralization of IFN-gamma and tumor necr osis factor alpha (TNF-alpha) partly attenuated IP-10 and Mig release, whil e anti-interleukin-12 (IL-12) and anti-IL-18 had a synergistic effect. Stim ulation with other bacteria or endotoxin also induced strong secretion of I P-10 and Mig. These data suggest that IP-10 and Mig are part of the innate immune response to bacterial infection. IP-10 and Mig may contribute to hos t defense in Th1-mediated host defense during infections by attracting CXCR 3(+) Th1 cells to the site of inflammation.