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Inflammatory mechanisms are involved in pathogenesis of atherosclerosis. During atherogenesis monocytes invade the vessel walland may interact with human vascular smooth muscle cells (SMC, thereby contributing to local pathogenesis by production of proinflammatory cytokines. Thus, we investigated the interaction of human mononuclear cells (MNC) and SMC. MNC or SMC were cocultured in vitro in one well, in the absence or presence of LPS (endotoxin. In parallel MNC, as well as SMC, were cultured in separate wells. The cytokine production was measured by ELISA and the IL-6 production of the cocultures was compared to the sum of the separately cultured cells. In the cocultures IL-6 production was synergistically enhanced, i.e. was 4- to 11-fold higher as compared to the sum of separate MNC and SMC cultures. Cocultured cells released even more (2-fold) IL-6 than SMC stimulated with maximal concentrations of IL-1α. Under serum-free conditions the synergism was still 40 ± 2% of the serum-containing conditions. No synergism was detected for fractalkine or IL-1 production. The synergism was mediated preferentially by soluble mediators, since it was still detectable in experiments with culture-inserts, separating the cells, but permitting exchange of soluble substances. The synergism was partially blocked by IL-1 receptor antagonist or IL-1β antiserum. Thus, locally produced IL-1 may be a player in the induction of the IL-6 synergism. Other soluble factors contributing to the synergism remain to be established. Furthermore, these results indicate, that interaction of cells in the tissue may be sufficient to induce IL-6 production, thereby contributing to pathogenesis of cardiovascular disease.
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J. Vasc. Biol. 42, Sup:2 (2005) p53