Effects of secretory leucocyte protease inhibitor on the production of the anti-inflammatory cytokines, IL-10 and transforming growth factor-beta (TGF-beta), by lipopolysaccharide-stimulated macrophages.

We studied the effects of secretory leucocyte protease inhibitor (SLPI) on the production of the anti-inflammatory cytokines, IL-10 and TGF-beta, by lipopolysaccharide (LPS)-stimulated macrophages, using half-sized SLPI (1/2 SLPI) containing the C-terminal domain (Arg58-Ala107). ELISA testing of macrophage culture fluids showed a temporary production of IL-10 by the macrophages in the early phase (24 h) after LPS stimulation at low (1 ng/ml) or high (10 microg/ml) concentrations. On the other hand, TGF-beta production was initiated after day 3 and progressively increased. 1/2 SLPI significantly increased IL-10 and TGF-beta production by macrophages in response to a low dose as well as a high dose of LPS. Reverse transcription-polymerase chain reaction analysis showed that 1/2 SLPI caused a significant increase in the expression of both IL-10 and TGF-beta mRNAs by LPS-stimulated macrophages. Thus, although the profile of macrophage TGF-beta production by LPS-stimulated macrophages is markedly different from that of their IL-10 production, SLPI causes an up-regulation of the production of these anti-inflammatory cytokines by LPS-stimulated macrophages.