In vitro anti-inflammatory activity of Phlebodium decumanum. Modulation of tumor necrosis factor and soluble TNF receptors.

The immunomodulatory activity of a standardized water soluble fraction of the fern Phlebodium decumanum (EXPLY-37) previously shown to have "in vivo" anti-inflammatory activity was analyzed "in vitro". This extract inhibited tumor necrosis factor (TNF) production by macrophages activated with lipopolysaccharide (LPS) or LPS plus interferon (IFN)-gamma. In contrast, nitric oxide (NO) and interleukin (IL)-1beta production were not affected in the same cultures, whereas IL-6 production was partially inhibited. More interestingly, EXPLY-37 increased the release of soluble TNF-receptor 2 (sTNFR2) and of IL-1R antagonist (IL-1Ra) but not of sTNFR1, by activated macrophages. EXPLY-37 had no effect on T lymphocyte activation, measured as proliferation as well as expression of early and late cell surface antigens CD69, CD25 (IL-2R-alpha) and CD71 (transferrin receptor) at the cell membrane. At the molecular level, EXPLY-37 did not inhibit the activation of the nuclear factor kappa B (NF-kappaB) transcription factor by TNF. In summary, EXPLY-37 has two anti-inflammatory activities "in vitro": it decreases TNF production and increases IL-1Ra and sTNFR2, which may be able to neutralize IL-1 and TNF activity, respectively.