Parasite-monocyte interactions in human leishmaniasis: production of interleukin-1 in vitro

Leishmania are obligate intracellular protozoa that parasitize mononuclear phagocytes. Because mononuclear phagocytes are also the primary source of leukocytic pyrogen and of lymphocyte-activating factor, both considered properties of interleukin-1 (IL-1), we investigated in vitro production of leukocytic pyrogen and of lymphocyte-activating factor from human monocytes infected with Leishmania tropica. Despite parasitization of 95% of cells, 24- and 48-hr culture supernatants and cell lysates derived from L. tropica-infected monocytes did not contain IL-1. Leishmania that were killed by freezing or by glutaraldehyde treatment similarly did not induce monocyte production of IL-1. Of importance is the observation that human monocytes infected with L. tropica for 6 hr and then challenged with a potent IL-1 inducer (Staphylococcus epidermidis) produced significantly less IL-1 than did uninfected monocytes that were similarly challenged (P less than .001). This difference was not affected by the addition of indomethacin to the cultures. In contrast, soluble immune complexes prepared with an excess of L. tropica antigen and rabbit antibody to L. tropica induced high levels of IL-1 production from normal monocytes. Neither antigen nor antibody alone incubated with monocytes led to significant production of IL-1, however. Thus, these studies suggest that despite leishmanial adherence to, entrance into, and replication within human monocytes there is little or no stimulation of IL-1 production. This may represent a parasite evasion mechanism that retards the development of protective immune responses in leishmaniasis.