Interleukin-6 changes deformability of neutrophils and induces their sequestration in the lung

Interleukin-6 (IL-6) is an important mediator of both the hepatic and the b one marrow components of the acute-phase response. Previous studies from ou r laboratory have shown that cells released into the circulation from the m arrow preferentially sequester in the lung. The present study was designed to examine the mechanism of this sequestration using a single dose of recom binant human IL-6 to stimulate the marrow in rabbits. Marrow release was mo nitored by labeling polymorphonuclear leukocyte (PMN) precursors in the mar row with the thymidine analogue, 5'-bromo-2-deoxyuridine (BrdU), 24 h befor e IL-6 treatment. This treatment caused a neutrophilia that was associated with the increase of circulating BrdU-labeled PMN (PMNBrdU) and morphometri c studies confirmed that PMNBrdU released from the marrow preferentially se questered in the lung microvessels compared to unlabeled PMN. IL-6 treatmen t increases PMN F-actin content (p < 0.05) that was not due to cell activat ion by IL-6. In vitro studies show that IL-6 treatment decreased the deform ability of circulating PMN (p < 0.05). These studies confirm that IL-6 trea tment causes an accelerated release of PMN from the bone marrow and shows t hat these newly released PMN have high levels of F-actin, are less deformab le, and preferentially sequester in lung microvessels.