HGE is characterized clinically by cytopenias, the pathogenesis of which is unknown. Because few cells are seen to be directly infected, we hypothesized that factors elaborated by HGE-infected cells might be important. Chemokines are powerful leukocyte chemoattractants capable, in minute concentrations, of suppressing hematopoiesis. We recently cultivated the HGE agent in HL-60 cells and further have shown that granulocytic differentiation of these cells by DMSO enhances infection (Klein, J Inv Med. 45:199A, 1997). Cytokines in HL-60 culture supernatants were measured in triplicate using modified sandwich ELISA assays on samples obtained sequentially after inoculation with the HGE agent. Production of both α and β Chemokines by infected cells was significantly elevated compared with uninfected controls in 3 independent experiments (table). In contrast, infected cells did not secrete TNF-α or IL-6. Chemokine levels peaked 48h after inoculation with HGE and correlated with the degree of susceptibility to infection (DMSO-treated > unstimulated HL-60 cells). Cells inoculated with heat-killed HGE did not secrete significant levels of chemokines. No endotoxin was detected using a Limulus assay. Mean Chemokine level (ng/106 cells): 48 h after inoculation with HGE MIP-1α MIP-1 β MCP-1 RANTES IL-8 Infected HL-60 8.74 11.68* 8.50* 3.58* 2.70 Uninfected HL-60 0.08 1.51 0.08 0.70 0.31 infected DMSO-tx 16.55 61.54 50.29* 28.4 39.11* uninfected DMSO-tx 0.22 2.51 3.95 5.04 0.31 (*p <0.05 vs. uninfected controls). The striking production of chemokines by HGE-infected cells is likely to be of pathogenic importance not only in the observed cytopenias, but also in mediating inflammation and host defenses.
|Original language||English (US)|
|Number of pages||1|
|Journal||Clinical Infectious Diseases|
|State||Published - Dec 1 1997|