Modulatory effect of prostaglandins on human monocyte activation for killing of high‐ and low‐virulence strains of Paracoccidioides brasiliensis

Summary The effect of indomethacin (Indo), a cyclo‐oxygenase inhibitor, on the monocyte‐mediated killing of a low‐ (Pb265) and a high‐ (Pb18) virulence strain of Paracoccidioides brasiliensis was examined. The Pb18 strain was not killed by either non‐activated or interferon‐γ (IFN‐γ) ‐activated human monocytes but these cells did show fungicidal activity if pretreated with Indo. In contrast with IFN‐γ, tumour necrosis factor‐α (TNF‐α) was very effective at stimulating the fungicidal activity of monocytes. While the low‐virulence strain, Pb265, could not be killed by monocytes, cells preincubated with IFN‐γ demonstrated fungicidal activity. The killing of this strain was also induced by pretreatment of monocytes with Indo. The results suggest a negative role for prostaglandins, which are synthesized via the cyclo‐oxygenase pathway, in the regulation of monocyte‐mediated killing of virulent and avirulent strains of P. brasiliensis and that TNF‐α generation during the fungus–monocyte interaction is more important in the killing of Pb265 than Pb18.