LTB4 and LTC4 are absent in the cerebrospinal fluid of human immunodeficiency virus type 1-seropositive persons with toxoplasmic encephalitis: evidence for inhibition of 5-lipoxygenase by Toxoplasma gondii.

Abstract

Previous studies on macrophages have shown that Toxoplasma gondii alters the metabolism of arachidonic acid with subsequent inability to generate leukotrienes (LT)s. LTB4 and LTC4 were analyzed in cerebrospinal fluid of 3 groups of human immunodeficiency virus (HIV) type 1-seropositive patients: with toxoplasmic encephalitis (TE) (n=10), with herpes simplex encephalitis (n=5), and without encephalitis (n=10) and in HIV-1-seronegative controls without inflammatory diseases (n=30) by specific immunoassays and gas chromatography-mass spectrometry. In HIV-1-seropositive subjects with TE, LTB4 and LTC4 were below the detection limit (<5.0 pg/mL) and thus significantly decreased (P<.01) compared with HIV-1-seropositive patients with herpes simplex encephalitis (LTB4, 148.5+/-47.6 pg/mL; LTC4, 116.4+/-36.9 pg/mL) and in those without encephalitis (LTB4, 46.1+/-16.8 pg/mL; LTC4, 48.3+/-21.3 pg/mL), and in controls (LTB4, 43.6+/-21.2; LTC4, 45.2+/-18.9 pg/mL). These results point to an essential role of inhibition of 5-lipoxygenase with subsequent failure of LT release as an important mechanism for the survival of T. gondii in vivo.