Silica enhancement of murine endotoxin sensitivity

Abstract

Silica has been used for many years as an agent which selectively alters macrophage functions and, as such, has been used to assess the role of macrophages in the immune response to a variety of microbial and chemically defined agents. Silica treatment of C3H/HeN mice 1 day before challenge with protein-free Escherichia coli endotoxin (lipopolysaccharide [LPS]) resulted in a marked increase in LPS sensitivity, as evidenced by accelerated signs of endotoxemia as well as a fourfold decrease in the LPS 50% lethal dose. The silica-mediated increase in responsiveness to LPS was associated with increased production of macrophage-derived soluble factors both in vivo (interferon) and in vitro (Interleukin 1; previously referred to as lymphocyte activating factor or LAF) upon endotoxin stimulation. These findings support the central role of the macrophage and its products in mediating endotoxic reactions.