COLONY-STIMULATING FACTORS ACTIVATE HUMAN MACROPHAGES TO INHIBIT INTRACELLULAR GROWTH OF HISTOPLASMA-CAPSULATUM YEASTS

Recombinant cytokines and colony-stimulating factors (CSFs) were tested for their abilities to activate human monocytes/macrophages (Mphi) to inhibit the intracellular growth of or kill Histoplasma capsulatum yeasts. None of the cytokines or CSFs or combinations of cytokines and CSFs activated Mphi fungistatic activity when they were added to Mphi monolayers concurrently with yeasts. In contrast, culture of monocytes for 7 days in the presence of interleukin 3, granulocyte-Mphi CSF, or Mphi CSF stimulated Mphi fungistatic (but not fungicidal) activity against H. capsulatum yeasts in a concentration-dependent manner. Optimal activation of Mphi by CSFs required 5 days of coculture, and the cultures had to be initiated with freshly isolated peripheral blood monocytes. Culture of monocytes with combinations of CSFs or addition of CSFs during the 24 h of coculture with the yeasts did not further enhance Mphi fungistatic activity for H. capsulatum. Addition of gamma interferon or tumor necrosis factor alpha to CSF-activated Mphi also did not enhance Mphi fungistatic activity. These results suggest that interleukin 3, granulocyte-Mphi CSF, and Mphi CSF may play a role in the cell-mediated immune response to H. capsulatum by enhancing monocyte/Mphi fungistatic activity.