IMMUNOMODULATING PROPERTIES OF THE ANTIBIOTIC NOVOBIOCIN IN HUMAN MONOCYTES

We show that the coumeromycin antibiotic novobiocin, a potent inhibito r of ADP ribosylation, prevents lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, and IL -10 secretion in human peripheral blood mononuclear cells. It shares t hese cytokine-suppressing properties with other inhibitors of ADP ribo sylation. We found that novobiocin prevents TNF-alpha production by in hibiting translation of the TNF-alpha mRNA. Elevated TNF-alpha levels in mice treated with D-galactosamine (GalN)-LPS or GalN-TNF were not r educed by novobiocin; however, the drug exhibited hepatoprotective pro perties. Novobiocin causes downregulation of the surface molecules on monocytes, among which CD14 was the most affected. The diminished expr ession of surface molecules was not observed on T and B lymphocytes, S imilar to other inhibitors of ADP ribosylation, novobiocin prevents LP S-induced phosphate labelling of gamma-actins.