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

Abstract

Infection by human granulocytic ehrlichiosis (HGE) is characterized clinically by cytopenias out of proportion to the number of cells seen to be infected 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 modified sandwich ELISA assays on samples obtained sequentially after inoculation with the HGE agent. All infected cells produced physiological concentrations of CC (monocyte chemotactic protein-1, macrophage inflammatory protein-1alpha and -beta, and RANTES) and CXC (interleukin [IL]-8) chemokines in amounts significantly greater than those produced by uninfected controls. In contrast, infected cells did not secrete the classic proinflammatory cytokines IL-1, IL-6, or tumor necrosis factor-alpha. The striking production of chemokines, powerful leukocyte chemoattractants capable of suppressing hematopoiesis, by susceptible target cells, is likely to be of pathogenic importance both in the observed cytopenias and in mediation of inflammation and host defenses during infection.