Modulation of tumor necrosis factor (TNF) production by interferon (IFN) in chronic hepatitis C (CMC): Relationship with the therapeutic response

149 UODULATION OF TIMOR NECROSIS FACTOR (TNF) PRODUCTION BY INTERFERON (IFR) IN CHRONIC HEPATITIS RELATIONSHIP WITS THE THERAPEUTIC SSSc (CHC): PONSE. E. Lsrres. J. CBIIII)S, A. csstills. H.P. Civeirs, J. Prieto. Dpto. of Medicine. University of Na“art-e. PamPlons. Spain. TNF is vity. IFN

P Potent monokine with antiviral setiis‘s” inducer of TNP production. A VPbioloricsl effects of TRP are medieted by I&. We studied the relationshipbetween TNF nroduction and the thersnsutic rssoonse to IFI in patients with WC. S&m TSF levels were dstermined in 19 patients before snd after eomplstion 12 months therapy with lymphoblastoidIFU. 11 patients normalized ALT levels st the end of tre&ent (responders. RI while in 8 patients N.T values remained high (non responders, NR). Seem TNF activity wee osssyed by maseuri"S cytotoxicity on L-929 cells. In ti s signifle&t increase in serum TNF activity wse observed bet-

rietv

of

ween basal and endtreatment vhluee (1.8 + 0.5 10.3 + 2.4 U/ml). In NR no sisnifieantohanres

ve

in TNi+ levels occurred during
150 ANTI-HUMAN LIVER CYTOCHROMR P-450 IA2 ANTIBODIES IN PATIENTS “IT” DIHTDSALAZINE HEPATITIS D. ~srrey, H. Rourdi. J. Natsf. J. Bernuau, D. GuenRerich, Ph. Iwssski, F.P. Pessayre, M. HBpiral Iiecker, Paris; u-75. Beau”=. H6pitsl Beaujon, Clichy, France; INSERH U-24, Biochemistry, Panderbilt Department of University, Nashville, U.S.A. Anti-liver microsome autoantibodies (anti-LM) dihydrslstine in ostients with are aresent The &pose of this study . was :o hepatitis. such antigen recognized by characterize the antibodies, and to assess their specificity. with dihydralazine Results; Sers of 5 patients hepatitis recognized a single protein of 53 kDs microsomes. This on immunoblots of human liver recognized by specific likewise Protein was

INBE~

anti-humsn with

OF INTERFERON+‘(IFN/) ON HEPATITIS B VIRUS (HBV) ANTIGENS EXPRESSION CONTRAST THAT WITH INTEKFEROS-&IN PRlMARYHEPATOCYTECULTURE

JYN Lau,VG Bai".NVNaoumov, HM Smith.GJMAlcxander,Roce:er Williams Liver Unit. King’s College Hospilal, London SE-59RS. UK IFNiC is of proven value in chronic HBV inlecrion. Ihe mode of aclion is uncerlain but may include enhanced rccognidon of HBsAg since in vitro treatment of hepatocytes increased dillercnrially the hepatoqte concentration of HBsAg and swilched Ihe localisalion of lhll anligen from dilfusc c}wplasmic to submcmbraneous. As measured hy serum HBV-DNA

IFNY

is also anti-dral

in chronic

HBV infcc,ion. but Ihe combination of IFNa and IFN IS no, adwnagcous. To determine ,he elfccl of IFNron HBJ anugcn cprcssion. hepaloqcs isolated from chronic HBV pal&us wxe Incubated in ,he absence or presence of IFNr(1 and IO units/ml) for I8 hours and antigen eqxcssion assessed by radioimmunoassay (RIA) or immunoqlochemisay using appropriate monoclonal andbodies. lntmcellular HBsAg measured by RIA of sonica!ed hepalocyla fell from 193 10 7.8 and 7.5 ng!2OO,C3Jcells \hilb !FN&l and IO unilsiml (p ~0.01 and pc0.001) resp’ctiwly and secreted HBs& wr, also reduced from 13 10 7.5 ng \*ith 10 w!!P!E! of !FNp (p ~0.01). lntrncellular HBeAg (cpmhtandsrd positive control) dropped loom

0.29 10 0.13 and 0.12 (p ~0.05)hutsecrcled HEzAg ws unaffected. On immunoslaincd q&pins. ,he proporlion oi hepa&yws conmining HBrAg. HBeAs. prc-S,. prc-S, also decrcascd

signiiiuntly

(p cO.05)

dlh fm r ;ncuha,bn. In~~accllular an,iScn~densiti& &a also reduced in ,hose posi,i\r: cells. In comrils, IO ,be cllcc, of IMO( in which prc-S, and HBsAg uwc cnhanccd. IFNt inhihitcd all the anliSen lcslcd. If the ekcl of IFNa is rehucd ,o enhanced HBsAg esprcssion. IFNY Ml no! be uscIul in combinxion wirh IFNOC.

IAZ.

and Anti-L>1

comigrated antibodies

ill-effect. _ in Co"clusio". Serum anti-Ll4autoanribodier dihydrslszine hepatitis ate patients with directed against human liver cytochrome P-450 IA2

152

EFFECTS

IA2 antibodies

human P-450

antibodies in immunoblots ‘cas absent in sers from patients with hepatitis A (n-51, hepatitis B hepatitis B + D (n-5). hepatitis caused (n-51, by other drugs (n-12) (including 2 cases vith chronic active hepatitis anti-LKM2 antibodies), with anti-LICMl antibodies (n-6). and 2 subjects without hepstic receivinn dihydrslszine but

and appear

151

P-450

aurified

ethoxyresorufin specifically inhibited phenacetin 0-deethylstion (2 reactions support:: to anti-W4 by P-450 IAZ). The band corresponding

to

be

specific

for

this

liver

fnjury.