1992). Evidence has now accumulated which indicates—Herakleitos that alternatively activated macrophages express a special set of molecules enabling them to actively participate in anti-inflammatory processes, tolerance induc-In the course of inflammatory reactions, proinflamma- tion, and healing. Recently, dendritic cells known as tory mechanisms are most important to guarantee elimi- specialized antigen-presenting cells (APC) supporting nation of the causative infectious, toxic, or allergenic Th1 differentiation have also been shown to undergo agents. It is mandatory, however, that inflammatory pro- alternative activation under certain conditions. Here we cesses, once induced, do not escalate but are again revisit Gordon’s concept of alternative activation of APC downregulated to allow healing. Therefore, proinflam- and show that it fits well with what is known as “supmatory and anti-inflammatory mechanisms must be acti- pressive” functions of APC (Figure 1). vated spatially and temporally in a finely tuned manner. The inflammatory processes in sepsis are a good exam- Molecular Repertoire of Alternatively ple for such a balanced interplay. Here, the causative Activated Macrophages agent is a microbial agent; however, massive secretion Alternative activation of macrophages may be induced of cytokines such as interleukin (IL)-1 or tumor necrosis by IL-4 and glucocorticoids as well as by other cytokines factor (TNF)-actually mediates the detrimental devel- such as IL-10, IL-13, and transforming growth factor (TGF)-, with similar effects. Alternatively activated macroopments. Via neuroinflammatory interactions, the septic phages express phenotypic and molecular characterisorganism tries to counteract the effects of these prointics that differ considerably from those of classically flammatory cytokines; finally, glucocorticoids are synactivated macrophages. Regulation and expression of thesized and secreted and may exert their pleiotropic inflammation-associated molecules and genes in macanti-inflammatory effects (Wilckens and De Rijk, 1997). rophages is regulated antagonistically by IL-4 and IFN,