Enhancement of immune complex clearance by TNF-alpha in a murine model

Recently, we presented evidence that lipopolysaccharide (EPS) treatment of BALB/c mice induces an enhancement on mononuclear phagocytic system functio ns, leading to a more efficient clearance of immune complexes (IC). In the present study we analyzed the role of tumor necrosis factor alpha (TNF-alph a), one of the earliest mediators released after LPS injection, in the clea rance of IC, Our results show that the enhancing effect of LPS on clearance can be partially reproduced by intravenous injection of sera from mice inj ected with LPS 1 h before. At this time point, the levels of TNF-alpha reac h a maximal peak of 240 +/- 73 U-50%/ml [TNF-alpha (+) serum]. However, ser a obtained after 4 h of LPS injection, with a TNF-alpha activity of 3.5 U-5 0%/ml [TNF-alpha (-) serum], did not exert any relevant effect on IG cleara nce. In addition, the effect of TNF-alpha (+) serum was completely blocked by preincubation with rabbit anti-TNF-alpha antibody. Moreover, the enhance ment of IC clearance can be similarly induced by administering murine recom binant TNF-alpha. Furthermore, the EPS-insensitive C3H/HeJ mice, which do n ot secrete TNF-alpha in response to LPS, showed a normal IC clearance after LPS injection. Taken together, these results strongly suggest that the enh ancement of IC clearance by LPS treatment could be mediated, at least in pa rt, by TNF-alpha. (C) 1998 Academic Press.