ALTERED PRODUCTION OF GM-CSF AND IL-8 IN CYTOMEGALOVIRUS-INFECTED, IL-1-PRIMED UMBILICAL-CORD ENDOTHELIAL-CELLS

The human cytomegaloviruses (HCMVs) appear to have the potential to di srupt production of hematopoietic cytokines. We examined the productio n of granulocyte/macrophage colony-stimulating factor (GM-CSF) and int erleukin (IL)-8 by cultured and CMV-infected human umbilical vein endo thelial cells (HUVECs) and compared this production with that of uninf ected cells. Endothelial cells are, among other things, an integral co mponent of human bone marrow stroma, and are responsible for productio n of factors that modulate the proliferation and differentiation of hu man hematopoietic progenitors. HCMV infection increased the production of GM-CSF in IL-l-primed HUVECs without altering GM-CSF levels in inf ected but unprimed HUVECs. However, this same virus was capable of cau sing increased production of the inhibitory cytokine IL-8. Both the vi ral pellet and the cleared viral supernatant appeared to contribute eq ually to the increased IL-8 and GM-CSF production, because each of the se preparations alone was capable of exerting only half the effect see n with whole virus preparations. That both live virus and soluble prot ein factors within the viral stock contributed to the enhancement in G M-CSF and IL-8 production was further confirmed by inactivation with e ither ultraviolet or heat treatment of the viral stocks. Although the identity of the factor within the HCMV stock that contributes to this effect remains unknown, studies conducted in the presence of neutraliz ing antibodies or polymyxin B ruled out a role for tumor necrosis fact or-alpha, IL-6, or endotoxin, all known inducers of GM-CSF. These stud ies indicate that HCMVs can exert both direct and indirect effects on the production of the hematopoietic factor GM-CSF and the inflammatory /inhibitory cytokine IL-8.