Immunomodulatory agent muramyl dipeptide (MDP) and seven of its analogues were tested for ability to counteract the toxic actions of lipopolysaccharide (LPS) in experimental mouse models. Female BALB/c mice were presensitized with Corynebacterium parvum (P. acnes) and given MDP or equimolar doses of one of its analogues after 2 weeks, followed by intravenous challenge with LPS 18 h later. This treatment produced a sharp increase in blood cytokine (TNF‐oc, IL‐la) levels 4 h after LPS administration followed by a decline to control values after 6 h. Four analogues, GMDP, threonylMDP, GMDPBenz and GMDPOBut, were able to reduce the level of cytokines induced with LPS. For most of the analogues, the higher doses reduced the levels of TNF‐a but slightly increased the concomitant IL‐lα levels. GMDP was the most effective compound tested in terms of reduction of TNF‐α and IL‐lα levels, as well as for reduction of the hypoglycaemia caused by the administration of LPS.
Human decidua in the third trimester of pregnancy contains at least four different cell types (stromal cells, macrophages, T-lymphocytes and granulocytes). The contributions of these cells to the overall function of the tissue are not known, although it is anticipated that both stromal cells and macrophages will produce the prostaglandins involved in labour. In addition, the decidua produces cytokines, but the cellular source has not been identified. As a first stage to addressing these questions, we have developed magnetic separation methods to obtain enriched populations of decidual macrophages which contain at least 5 x 10(6) cells. We found that a preparation of up to 10(7) cells which are up to 80% pure (as assessed by a fluorescence-activated cell sorting procedure) and approximately 90% pure (as assessed by immunocytochemistry) can be obtained reliably with this method. These cells are viable for at least 48 h in culture after the enrichment procedure, and produce prostaglandins after stimulation with interleukin-1 beta.
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