Pathobiology 1999;67:291–293 The Role of Cytokines in Monocyte Apoptosis H.-D. Flad a E. Grage-Griebenow a F. Petersen a B. Scheuerer a E. Brandt a J. Baran b J. Pryjma b M. Ernst a a Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany; b Department of Microbiology and Immunology, Institute of Molecular Biology, Jagiellonian University, Cracow, Poland Dr. H.-D. Flad Department of Immunology and Cell Biology Research Center Borstel D–23845 Borstel (Germany) ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2000 S. Karger AG, Basel 1015–2008/99/0676–0291$17.50/0 Accessible online at: www.karger.com/journals/pat Key Words Apoptosis W Monocytes W TNF· W GM-CSF W Platelet factor 4 Abstract Survival or apoptosis, activation and differentiation, phagocytosis and antigen presentation, migration or participation in granuloma formation are features of freshly recruited blood-borne monocytes in the local environment. In this presentation we describe that hu- man monocytes undergo spontaneous apoptosis in vitro which involves Fas/FasL interactions, and that proinflam- matory cytokines such as tumor necrosis factor-· (TNF·), interleukin-1ß and granulocyte-monocyte-colony-stimu- lating factor prevent spontaneous apoptosis. In vitro infection of purified monocytes with low numbers of Mycobacterium tuberculosis H37Rv prevents sponta- neous apoptosis. The apoptosis-preventing effect is cor- related to the release of TNF· and not due to phagocyto- sis per se. Furthermore, the minor subset of CD64-nega- tive monocytes is found to be less susceptible to recall antigen-activated CD4-positive T cell-mediated apopto- sis than CD64-positive monocytes. Finally, recent find- ings of our group indicate that the chemokine platelet factor 4 protects monocytes from spontaneous apopto- sis and induces the differentiation of monocytes into macrophages. From these findings we conclude that monocyte recruitment, their survival, their differentiation and their functional activity at the site of inflammation are regulated by a cytokine network which needs to be further analyzed in order to design strategies for immune intervention. Copyright © 2000 S. Karger AG, Basel Introduction Unstimulated monocytes and macrophages cultured at low serum concentrations undergo spontaneous apoptosis in vitro. In recent years various mechanisms have been discovered by which monocytes and macrophages are able to escape spontaneous apoptosis. In this article we briefly review our findings related to the role of certain cytokines with antiapoptotic activity. Proinflammatory Cytokines Abrogate Spontaneous Apoptosis of Monocytes Spontaneous apoptosis of human monocytes in vitro was prevented by tumor necrosis factor-· (TNF·), inter- leukin-1ß and granulocyte-monocyte-colony-stimulating factor (GM-CSF) [1]. Interestingly, in vitro infection of purified human monocytes with low numbers of Myco-