Induction of prostaglandin E2 by human monocytes infected with Mycobacterium avium complex-modulation of cytokine expression

Prostanoids, including prostaglandin E₂ (PGE₂), suppress macrophage effector functions against Mycobacterium tuberculosis. PGE₂ production by monocytes infected with Mycobacterium avium complex (MAC) and its effects on intracellular mycobacterial growth were examined. Freshly obtained monocytes from healthy subjects were stimulated with lipopolysaccharide or 10⁷ organisms/mL of 4 MAC strains. PGE2 production in monocyte supernatants peaked at 48 h. Significantly higher levels of PGE₂ were produced by monocytes infected with the mixed rough-smooth, flat, and transparent (SmT) morphotype strain 86m2096 (26.8 ± 5.2 ng/mL) than by the more virulent LR114 SmT morphotype strain (2.4 ± 0.6 ng/mL; P <.05, paired t test). When infected monocytes were incubated with 1 μg/mL indomethacin (IM) for 2 days and then further stimulated with interferon-γ, no effect on intracellular MAC growth was evident. IM increased tumor necrosis factor-α (1.7 ± 0.4 vs. 2.3 ± 0.3 ng/mL; P = .005, paired t test) but not interleukin-1β (8.2 ± 1.7 vs. 8.7 ± 2.1 ng/mL, P = .34) production by monocytes stimulated with lipopolysaccharide. These data suggest that MAC-induced PGE2 expression may modulate cytokine production and intracellular parasitism.