The agent of human granulocytic ehrlichiosis induces the production of myelosuppressing chemokines without induction of proinflammatory cytokines

Infection by human granulocytic ehrlichiosis (HGE) is characterized clinica lly by cytopenias out of proportion to the number of cells seen to be infec ted directly. To study the pathogenic role of inflammatory mediators in HGE infection, cytokine production by untreated and dimethyl sulfoxide-treated HL-60 cells, which demonstrate enhanced infection because of granulocytic differentiation, and by normal bone marrow cells was measured using modifie d sandwich ELISA assays on samples obtained sequentially after inoculation with the HGE agent. All infected cells produced physiological concentration s of CC (monocyte chemotactic protein-1, macrophage inflammatory protein-1 alpha and -beta, and RANTES) and CXC (interleukin [IL]-8) chemokines in amo unts significantly greater than those produced by uninfected controls. In c ontrast, infected cells did not secrete the classic proinflammatory cytokin es IL-1, IL-6, or tumor necrosis factor-alpha. The striking production of c hemokines, powerful leukocyte chemoattractants capable of suppressing hemat opoiesis, by susceptible target cells, is likely to be of pathogenic import ance both in the observed cytopenias and in mediation of inflammation and h ost defenses during infection.