Gamma-Interferon (γ-IFN) production by peripheral blood mononuclear cells (PBMC) in chronic non-A non-B viral hepatitis (CNANBH) patients

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GAMMA-INTERFERON ( ~ - I F N ) PRODUCTION BY PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) IN CHRONIC NON-A NON-B VIRAL HEPATITIS (CNANBH) PATIENTS. S~Morte, M.Serrano~ A . C a s t i I I a , M . P . C i v e i r a ~ J . P r i e t o , Dpt. o f M e d i c i n e , U n i v e r s i t y C l i n i c o f N a v a r r e , Pamp]ona, Spain.

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The n~echanlsm responsible for chronlc liver ie~Ion in ~o}IA, nonB virus {as} infection 15 un~l}ow but It Is postulated that an ~m~unolog~c d~sturbance n~ayplay a role ~n the pathogenesls of thls dlsease, ;-[FN is a !y~pho~ne ~ t h ~ult~pi~ ~mmunoregulato~'y actLons and It also has a~tlv£ral effects, Ve have studied 20 patlen~s wlth CNANBHand 27 controls, PBMCwere ~solated and stimulated with ConA at 20 pg/2,5,10 ~ cells/~l of RPMI, I% total calf serum, Attar 48 h, incubatlon at 3ICC, 5%C0=, superna~ants were stored at -70~C, ~-IFN levels were evaluated by the cytoprotect[ve actlvi~y on EMC 91rus-lnfected He£a cells, The patients produced ~lore ~-!FN ~l,33±0,21; 7=SEM) than controls ~0,7)IU,08}~p~0,01~, A~on9 patlents there were two groups; those whose ]-IFN production was over 7 + 2SO of controls tQroup l, n=7) and those wlth horn,a! IFN production ~@roup 2, n=13), 8roup I had ~ore c:rculat:ng C04 + cells ~43,70~4,65) and lower ALT levels t69.85±16.94~ than Group 2 (~2,10±3,06, p;O,05 ~nd 124,53±14,99, p:0,05 respectively), There was a poslt~ve correlation between ~-!FN production and ALT levels ~r=0,57, p<0,01), Group I had a Knodell's Inde;, and a peaceB~al necrosis :ndex luwer than Group 2 (pK0,05 for both p~,'a~eters), Conc~uslon, Patients w~th CNANBHe~hlb~ng i~creased production of ~-IFN b~ PBMChave a ~llder d~sease than those ,~an~fest~ng nor~:al levels of ~-IFN synthesis, Th~s fact suggests that the natural history of CNANBHdeoend~ on the host's ~mB~uneresponse, including the ant~v~ral action of IFN,

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STUDY ON THE MOLECULAR MECHANISM OF THE DECREASED LIVER SYNTHESIS OF ALBUMIN IN INF LAMMAT ION HJ Moshage, JAM Janssen, JH Franssen JCM Hafkenscheid*, SH Yap. Div. of G.I. and Liver Dis, *div. of Clinical Chemistry, Dept. of Med. St. Radboud Univ. Hospital, Nijmegen, lhe Netherlands.

In inflammatory diseases, hypoalbuminaemia is not an unfrequent r~nding. However, little is known about albumin synthesis under this condition. Using the [ C]-carbonate technique of McFarlane we have measured the albumin synthesis in four patients with inflammatory diseases (table 1). Since inflammation causes a decreased albumin synthesis which could not be related to a reduced amino acid supply, we have used in vivo experiments in rats and in primary cultures of rat hepatocytes to further elucidate the possible molecular mechanism. In rats with turpentine-induced inflammation, serum albumin and liver albumin mRNA levels were markedly decreased, lhese changes could not be reproduced by administration of fibrinogen- or fibrin-degradation products and of several hormones such as corticosteroids. However, monocytic products obtained from rabbits with a glycogen induced-peritonitis, of which the active principle is interleukin-I (IL-1), a 15 KD protein, reduced the albumin synthesis and liver albumin messenger RNA content in rats in vivo and in primary cultures of rat hepatocytes (table 2). Furthemore, the decreased liver albumin mRNA content in vivo and in vitro could be respectively partially and completely abolished by administration of--antibo-Edies against the 15 KD fraction. These findings suggest that monocytic products play an important role in the reduced albumin synthesis during inflammation. Table 1:pat. alb. synth, serum alb. Table 2:relative level of alb.mRNA in primary cull 14.0 g/24h 29.3 g/l - tures of rat hepatocytes 2 14.3 29.1 culture medium alb.mRNA level 3 12.7 25.8 without IL-1 100% 4 12.6 )1.2 with IL-I (200 ~:g/ml) 49+10% C(n:20)21.9~-6.6 44-55 with IL-1+antibodies 100%

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