The Journal of Immunology, Vol 152, Issue 9 4604-4611, Copyright © 1994 by American Association of Immunologists

ARTICLES

Fc gamma receptor cross-linking down-regulates IL-1 receptor antagonist and induces IL-1 beta in mononuclear phagocytes stimulated with endotoxin or Staphylococcus aureus

CB Marsh, HA Pope and MD Wewers
Division of Pulmonary and Critical Care Medicine, Ohio State University Hospitals, Columbus 43210.

The cross-linking of monocyte Fc gamma R is a potent stimulus for IL- 1ra production but does not induce IL-1 beta. However, during systemic infection, IgG-coated bacteria can activate mononuclear phagocytes via both cell wall components and opsonized IgG. Therefore, we analyzed the effect of combinations of Fc gamma R cross-linking and bacterial cell wall components on mononuclear phagocyte IL-1 beta and IL-1ra production. Human mononuclear cells and monocytes were cultured either alone or with combinations of immobilized IgG, LPS, or heat-killed Staphylococcus aureus (HKSA). Cells cultured on immobilized IgG released large amounts of IL-1ra but no detectable IL-1 beta. In response to LPS, mononuclear cells released IL-1ra at 1000-fold lower doses of LPS than was required to induce IL-1 beta. However, when measured in the presence of immobilized IgG, the LPS sensitivity for IL- 1 beta release increased 100-fold, whereas IL-1ra release correlated inversely with the LPS dose. Furthermore, HKSA, a nonendotoxin stimulus, affected mononuclear cell IL-1 beta and IL-1ra release similarly. In addition, polymyxin B, a specific endotoxin inhibitor, blocked the LPS, but not the HKSA-induced changes in IL-1 beta and IL- 1ra secretion, irrespective of immobilized IgG co-stimulation. In summary, these results suggest that mononuclear phagocyte stimulation with immobilized IgG favors IL-1ra over IL-1 beta production. Conversely, the addition of LPS or HKSA to the Fc gamma R-stimulated cells augments IL-1 beta but suppresses IL-1ra production.

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