Dilinoleoylphosphatidylcholine selectively modulates lipopolysaccharide-induced Kupffer cell activation

Polyenylphosphatidylcholine (PPC), a mixture of polyunsaturated phosphatidy lcholines extracted from soybeans, protects against alcoholic and non-alcoh olic liver injury. Because Kupffer cells mediate liver injury, we hypothesi zed that PPC may modulate their activation. The activation of Kupffer cells by lipopolysaccharide (LPS) leads to an enhanced production of cytokines. Among these, tumor necrosis factor-alpha. (TNF-alpha) exerts mainly a hepat otoxic effect, whereas interleukin-1 beta (IL-1 beta) appeals to be hepatop rotective. The present study evaluated whether dilinoleoylphosphatidylcholi ne (DLPC), the main component of PPC (40% to 52%), affects LPS-induced Kupf fer cell activation in vitro. For comparison, palmitoyl-linoleoylphosphatid ylcholine (PLPC), the other major component of PPC (23% to 24%), and distea roylphosphatidylcholine (DSPC), the saturated counterpart of DLPC, were als o tested. Rat Kupffer cells were cultured in serum-free RPMI-1640 medium co ntaining 10 mu mol/L of either DLPC, PLPC, or DSPC in the presence or absen ce of LPS (1 mu g/ml). After 20 hours in culture, the media were collected for cytokine measurements by enzyme-linked immunosorbent assays. LPS signif icantly stimulated TNF-alpha and IL-1 beta production by 62% and 328%, resp ectively. Treatment of Kupffer cells with LPS plus DLPC decreased the produ ction of TNF-alpha by 23% (12.17 +/- 1.83 pg/ng DNA vs 15.72 +/- 2.74 pg/ng DNA, P < .05, n = 6) and increased that of IL-1 beta by 17% (1.80 +/- 0.16 pg/ng DNA vs 1.54 +/- 0.08 pg/ng DNA, P < .05, n = 6). No effect of PLPC o r DSPC on LPS-induced TNF-alpha or IL-1 beta generation was observed, there by illustrating the selective effect of DLPC in this process. Thus DLPC sel ectively modulates the LPS-induced activation of Kupffer cells by decreasin g the production of the cytotoxic TNF-alpha while increasing that of the pr otective IL-1 beta. This dual action of DLPC on cytokines may provide a mec hanism for the protective effect against liver injury, but its significance still needs to be determined by in vivo studies.