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Individual Cell Analysis of the Cytokine Repertoire in Human
Immunodeficiency Virus-1-Infected Monocytes/Macrophages by a
Combination of Immunocytochemistry and In Situ Hybridization
Ruth Esser,
Wolfgang Glienke,
Reinhard Andreesen,
Ronald E. Unger,
Marina Kreutz,
Helga Rübsamen-Waigmann, and
Hagen von Briesen
From Georg-Speyer-Haus, Frankfurt am Main, Germany; the Department of
Hematology and Oncology, University of Regensburg, Regensburg, Germany;
the Neurological Institute (Edinger Institute), University of
Frankfurt/Main, Germany; and Bayer AG, Pharma Research Center,
Wuppertal, Germany.
The expression of many cytokines is dysregulated in individuals
infected with the human immunodeficiency virus-1 (HIV-1). To determine
the effects of HIV-1 infection on cytokine expression in individual
cells (at the single cell level), we investigated the intracellular
levels of proinflammatory cytokines (tumor necrosis factor [TNF]- ,
interleukin [IL]-1 , IL-6, and IL-8) and hematopoietic growth
factors (granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF]) in monocyte-derived macrophages, mock-infected, or infected with HIV-1 by
immunocytochemical staining for cytokine protein and compared this with
secreted cytokine levels as determined by specific enzyme-linked
immunosorbent assay (ELISA). No difference in the frequency or
intensity of cell-associated immunocytochemical cytokine staining could
be observed between HIV-1 and mock-infected cells even though the level
of secreted proinflammatory cytokines increased and the hematopoietic
growth factors decreased in HIV-1-infected cultures. Furthermore,
equal expression of cytokine mRNA was observed in all cells in the
culture regardless of whether the cells were productively infected with
HIV-1 as determined by double-labelling immunocytochemical staining for
HIV-1 p24 antigen and in situ hybridization for cytokine mRNA
expression. These results indicate that HIV-1 infection results in
dysregulation of intracellular cytokine mRNA expression and cytokine
secretion not only in HIV-1-infected cells, but also through an
indirect way(s) affecting cells not producing virus.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4752-4760
© 1998 by The American Society of Hematology.
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