IgG-coated erythrocytes augment the lipopolysaccharide-stimulated increasein serum tumor necrosis factor-alpha

Previous studies have shown that the injection of IgG-coated erythrocytes ( EIgG) caused an increase in the mortality rate due to bacterial lipopolysac charide (LPS). This observation led to the present evaluation of the effect of EIgG on the LPS-stimulated increase in serum tumor necrosis factor-alph a (TNF-alpha) levels and TNF-a secretion by macrophages. The prior injectio n of EIgG augmented the increase in LPS-stimulated serum TNF-alpha levels n inefold at 1 h after LPS. Serum TNF-alpha levels were augmented when LPS wa s injected 2 or 6 h after EIgG but not at 0.5 or 12 h after EIgG. Complemen t activation caused by EIgG may contribute to the priming for TNF-alpha, be cause activation of complement with cobra venom factor caused a threefold a ugmentation of the LPS-stimulated serum TNF-alpha levels. Isolated macropha ges that had ingested EIgG or were adherent to immobilized IgG; showed augm ented TNF-alpha secretion in response to LPS. Thus clearance of immune comp lexes from the blood can augment the LPS-stimulated increase in serum TNF-a lpha levels that is due, in part, to complement activation and signaling vi a Fc gamma R.