Scand. J. Immunol. 30, 363-367, 1989 Immune Dysfunction in Primary Biliary Cirrhosis II. Increased Production of Prostaglandin E M, CHIRICOLO, M. LENZI. F. BIANCHI. C. FRANCESCIII G. BARTOLINI, M. ORLANDI. V. TOMASI & F. LICASTRO Department of Experimental Pathology. Institute of Clinical Medicine, and Department of Experimental Biology, University of Bologna, and Institute of General Pathology, University of Modena. Italy Chiricolo, M., Lenzi. M., Bianchi. F., Franceschi. C, Bartolini. G.. Orlandi, M.. Tomasi. V. & Licastro, F. Immune Dysfunction in Primar>' Biliary Cirrhosis. II. lncrea.sed Production of Prostaglandin E. Scand. J. Immunol. 30, 363 367. 1989 In a previous study we observed that after in vitro trealment with indomethacin, lymphocyte response to phyiohacmagglutinin (PIIA) in primary biliary cirrhosis (PBC) patients was higher than that of controls. We know that indomethacin aiso inhibits prosianoid production, and thus in theprescni work we directly measured prostaglandin F; (PGE;)and thromboxane B:(TXB;) production by mononuclear cells and moniK-ytes from 12 PBC patients, 11 control subjects, and three control disease patients (alcoholic cirrhosis. AC). PHA-stimulated enriched monocytes from PBC patients produced approximately Ihreefold more PGE; {after 48 h of culture) than did normaland AC monocytes (P< 0.05). TXB; production was similar in all j;roups studied Wo ai.so made cultures in which PBC-purilied lymphocytes proliferated better than PBC mononuclear cells (i.e. lymphocytes plus nuinoeytes). Thus, a monocyte population producmg PGE; could be responsible, at least in part. Ibr ihe hyporesponsiveness to PIM observed in PBC patients. Marietta Chiricolo. PhD. Pipariimentti di Paialogia SperimentaJe. Universita di Bologna. Via S. Giacomo 14. 40126 Bologna. Italy Primary biliary cirrhosis (PBC) is a chronic progressive liver disease frequently associated with humoral and cellular immunological abnor- malities [9. 18, 21, 30]. In a previous study we found that indometha- cin significantly increased the phylohacmagglutl- nin (PHA)-.stimuUiled response of peripheral hlood lymphocytes from PBC patients [I8|. This increase was higher in PBC patients than in age- and otherwise matched controls. For this reason we have suggested that the impaired PHA- induced response of lymphocytes from PBC patients could he ascribed, at least in part, to an increased production nf soluble factors with suppressive effect on lymphocyte proliferation and sensitive to the modulation by indomethacin. These factors arc thought to belong to the family of arachidonic acid products, namely prostaglan- din E (PGE). PGE is an important local hormone produced by monocytes and macrophages 13], with a modu- latory role in T- and B-cclI proliferation and differentiation. Goodwin ct al. [10] observed that low doses of PGE inhibit lymphocyte proliferation induced by PHA and concanavalin A (Con A). Other authors have reported that PGE suppresses lymphocyte mitogeti proliferation [II], antigen response [31], cytotoxic cell production [6J. lymphocyte migra- tion |29], and lymphokine production. In particu- lar, the production of interleukin 2 (IL-2) has been reported to he decreased by PGE (25]. In this study we directly measured the produc- tion of PGE and thromboxane B:(TXB;.a stable metabolite of TXA;) in PHA-activated mononuc- lear cells and enriched monocyte cultures from PBC patients, control disease patients and nor- mal controls. 363