Phenotypic and functional characteristics of macrophage-like cells differentiated in pro-inflammatory cytokine-containing cultures

Previous studies have demonstrated an infiltration of monocytes and increas ed levels of IL-1 beta and TNF-alpha in some chronic inflammatory tissues. Interleukin-1 beta and TNF-alpha are capable of protecting monocytes from s pontaneous apoptosis and thus maintain their viability in vitro. To study t he possible effects of these cytokines on the differentiation and function of recruited monocytes, a model has been developed in which monocytes isola ted from human peripheral blood were differentiated into macrophages in ser um in the presence or absence of IL-1 beta or TNF-alpha. Monocytes cultured with IL-1 beta and TNF-alpha underwent substantial changes in morphology, similar to those observed in monocytes undergoing differentiation into macr ophages. The cultured cells increased in size and vacuolization and their c ontent of acid phosphates increased 10-fold. Although they exhibited the mo rphological characteristics of macrophages, monocytes matured in the cytoki nes differed functionally from those cultured in serum in a lower expressio n of HLA-DR, lower ability for triggering the proliferation of allogeneic l ymphocytes, higher expression of mannose receptor and greater production of superoxide and TNF-alpha. This data suggests that IL-beta and TNF-alpha di rect monocyte differentiation into macrophages with a reduced antigen-prese nting and an increased pro-inflammatory factor-releasing phenotype. Elevate d levels of IL-beta and TNF-alpha in the inflammatory tissues may therefore not only prolong the survival of recruited monocytes, but maintain them in an inflammatory state.