204 S-ADENOSYLMETHIONINE INflIBITS COLLAGEN SYNTHESIS BY HUNAN FIBROBLASTS IN

VITRO.

A. Casini, E. Banchetti, S. Milani, C. Surrenti Unit~ di Gastroenterologia,

Universit~ di Firenze, Firenze, Italy.

Previous experimental studies have indicated that S-adenosylmethionine (SAMe) exerts

hepatocytoprotective and anticholestatlc activities (Toxicol Lett 1986; 32: 97-106). In

order to clarify whether thls molecule has also antifibrotic properties, we evaluated

its pharmacological effects on human fibroblasts in vitro. Accordingly, fibroblasts

between 5 and i0 subcultures were incubated for 24 hrs with different SAMe

concentrations (from 0.005 to 155 uM). Fibroblast proliferation measured by

incorporation of labelled thymidine was not affected by SAMe in the range of the tested

concentrations. Moreover, cell viabillty assessed by trypan-blue exclusion test was

greated than 98% in all cultures, without any difference between SAMe and control

cultures. Collagen synthesis estimated by HPLC measurement of hydroxyproline in both

medla and cells was not modified by SAMe concentrations lower than 0.5 uM. On the other

hand, SAMe concentrations higher than 0.5 uM slgnificantly (p < 0.01) reduced collagen

synthesls as compared with untreated controls. This effect was not dose-dependent. In

conclusion, this study indicates that SAMe addition to fibroblasts in the range of

concentrations whlch can be found in vivo in the liver (up to 70 uM) induces a marked

decrease (about 50% of control value) in collagen synthesis in absence of any effect on

cell prolJferatlon and viability. These flndings suggest to further investigate the

potential antifibrotic role of SAMe in hver dlseases.

205 MONOCYTE FUNCTION IN CHRONIC NON-A,NON-B HEPATITIS (NANBH): RELATIONSHIP WITH THE ACTIVITY OF THE LIVER DISEASE.

A. Castilla, M.Serrano, S.Morte, M.L.Subir$, M.P.Civeira, J.Prieto, Dpt. of Internal Medicine,University Clinic of Navarra, Pamplona, Spain.

The monocyte-macrophage ceil llne is responslble for actlvatlon of cellular Immunlt? and plays an important role in virus clearance, We investigate monocyte fucntlon in 26 patients with CNANBH and 22 healthy controls, Interleukln I (IL-I) production by perlpheral blood mononuclear cells £PBMC~ was stlmulated with LPS and tested for the abl l l ty to induce mouse thymocytes proliferation, C3b receptor ~C3R) and DR molecules were analyzed in denslty flotatlon-purlfled monocytes by EAC rosettlng and indlrect l~munofluorescence us,ng OKIa-I antibody, Monocyte phagocytlc funct,on was evaluated by C,alblcans ingestion, Gamma interferon £1-[FN) synthesis by ConA-stlmulated PBMC was estlmated by the cytoprotectlve activity on EMC vlrus-lnfected Hela cells, The number of N~ cells was studied with Leu II antlbody and NK activity using ~-G62 cell llne, Patlents could be divided according to the level of IL-I production, Group l (n=l~) produced IL-l above the normal range (219 Ulml), whereas Group 2 (n=lS) secreted normal levels, Phagocytosls and e~presslon of C~R and DR were reduced in Group 2 as compared either with controls ~p~O,OOI, p<O,O01 and pCO,OOS respectively) or Group l (p<O,Ol, p<O,O5 and p<O,Ol), ~-[FN synthesis was higher in Group I (i,87±0,43, x±SEM)than in Group 2 (0,96±0,20, p<O,O5) or in controls ,0,73±0,08, pU),OOl) and there was a lineal correlation (r=0,67, p<O,O01) between levels of IL-I and ~-IFN production, NI: cells and activity were decreased in Group 2 as compared with controls or with Group i, Total Knodell's, intralobular degeneration and perlportal necrosis indexes were lower in Group I (p:O,02, p~O,05 and p(O,OS respectively), In conclusion, th*s study suggests that in CNANBH the functional state of the monocytes can be of central importance in activation of ~echanisms that control viral replication and modulate the intensity of the liver disease,

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