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

Recently, we presented evidence that lipopolysaccharide (LPS) treatment of BALB/c mice induces an enhancement on mononuclear phagocytic system functions, leading to a more efficient clearance of immune complexes (IC). In the present study we analyzed the role of tumor necrosis factor alpha (TNF-alpha), one of the earliest mediators released after LPS injection, in the clearance of IC. Our results show that the enhancing effect of LPS on clearance can be partially reproduced by intravenous injection of sera from mice injected with LPS 1 h before. At this time point, the levels of TNF-alpha reach a maximal peak of 240 +/- 73 U50%/ml [TNF-alpha (+) serum]. However, sera obtained after 4 h of LPS injection, with a TNF-alpha activity of 3.5 U50%/ml [TNF-alpha (-) serum], did not exert any relevant effect on IC clearance. In addition, the effect of TNF-alpha (+) serum was completely blocked by preincubation with rabbit anti-TNF-alpha antibody. Moreover, the enhancement of IC clearance can be similarly induced by administering murine recombinant TNF-alpha. Furthermore, the LPS-insensitive C3H/HeJ mice, which do not secrete TNF-alpha in response to LPS, showed a normal IC clearance after LPS injection. Taken together, these results strongly suggest that the enhancement of IC clearance by LPS treatment could be mediated, at least in part, by TNF-alpha.