IL-1beta as a determinant in silica-induced cytokine responses in monocyte-endothelial cell co-cultures

Alveolar macrophages and endothelial cells are both involved in lung inflammation and remodeling of lung alveolar structures. In the present study, monocytes (precursors for macrophages) were exposed to crystalline silica and examined for pro- and anti-inflammatory cytokine responses in non-contact co-cultures with endothelial cells. The time courses for silica-induced release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-8 both from co-cultures and monocyte mono-cultures showed an early peak at 5-10 h, almost no response at 20 h, and a strong increase at 43 h. At 43 h, co-cultures also showed strongly increased IL-6 levels. Steady-state levels of mRNA roughly exhibited the same pattern of early up-regulation and reduced levels at 20 h. Compared with monocyte mono-cultures, silica induced a strong release of IL-1beta, IL-6, and IL-8, but not of TNF-alpha, after 43 h in co-cultures, whereas at 5 and 10 h a significant difference was only observed for the silica-induced IL-8 response. An antagonist to the IL-1 receptor strongly reduced IL-6 and IL-8 levels, whereas antibodies to TNF-alpha increased the levels of IL-1beta and IL-8. Thus, IL-1beta is suggested to be an important triggering factor that determines the silica-induced release of several of the other cytokines in this co-culture system.