Oral Sessions / Parasitology Intematiod 264 O-0528 47 (Suppl.) (1998) 133-281 0-Os30 UP-REGULATION OF CYTOKlNES IN GLOMERULONEPHRITIS ASSOCIATED WlTH YURINE MALARIA INFECTION PERIPHERAL LYMPHOCYTE SUBSETS AND SERUM INPLAMMATORY MEDIATORS FROM PATIENTS WITH ACUTE UNCOMPLICATED FAEIPARUM MALARIA shpia Mzi?. Lin P-R*, Hung C-C** *National Defense Medical Center and **National Taiwan Li Ruimei*, AU Kara”, R Sinniah’ ‘Department of Pathology, and * School of Biological Sciences, National University of Singapore, Singapore Univ&tyHoqital,Taipei,Taiwan Glomerulonephritis (GN) is one of the major manifestations in malaria infection, and multiple factors have been implicated in the pathogenesis of glomerular injury. The role of cytokines in malaria esso&ted glornelulonephritis has not been clearly dafined. To study the importance of cytokines in malaria nephritis, we investigated the expression of TNF-a, IL-la, 11-6, IL-10 and GMCSF in kidneys acutely infected with murine malaria parasite P. berghei ANKA in C!37BL/6J mice. 36 kidneys taken from 5 groups of mice on days 5, 10, 15, 20 post-infection, and normal controls were used for cytokiie analysis. Elevated levels of mRNA specific for these cytokines in infected kidneys after day 5 postinfection were demonstrated by RT-PCR analysis. Kidney sections stained with specific antibodies against TNF-a, IL-la, 11-6, IL-IO and GM-CSF by immunohistochemistry, showed that the staining for these cytokines on the glomeruliwas positive from day 10 post-infection. and increased progressively, mainly in the infiltrating macrophages and the glomefular rnesangium. Strong correlatiin was found between the expression of TNF-a with IL-6, and IL-la with IL-6 The expression’ of TNF-a. IL-la, 11-6,. and IL-IO also strongly correlated with the severity of proteinuna. Our findings show upregulation of cytokines in glomenrlonephritis during murine malaria infection. sub~ulatiotLs,saumkvelsofey&ncs,andadbesioninokc& All patients tecovaed completely aftexa cuurse of I-day quinine (reatment. Ratios of CD4+:CD8+ lymphocytes in these patients were markedlymduccd (0.3 - 0.6) before and dutig the treatment, l O-0529 KlNEilCS OF LYMPHOCYTE SUBSETS IN PERIPHERAL BLOOD OF JAPANESE MACAQUES DURINGTHE COURSE OF INFECTION WITH mw COAlNEyl MatsurotoJ. Kawai S, Kirinoki M, Chigusa Y, *‘Suzuki * 2Aikawa M and Matsuda H Medicine, ‘1Department with but returned to a normal value (0.9 - 1.2) l-2 weeks after rzeatmeaf The populations of both activated T &ells (CD3+HLA-DR) and naturalkiller (NK.) cells (CD3TD16+CD56+) increased by 50100% throughoutthe course of acute illness but decrea& to tbe normalrangeafterdeatment Serumlevels of tumor nuxosis faetora, interleukin-1(ILl), and IL-6 in serumimxased signifiiantly in the acutephasebut not detectablein the convalescentphase. Serum levels of E-se&tin, vascular celI adhesion molecule-l. and intercellularadhesionmolecule-l were highly elevated in the acute phase while normal levels of these adhesion molecules were observed 4-8 weeks after treatment. While mild increases of serum interferon-y and IL 10 was only noted in the acute phase, levels of both IL-2 and IL-4 were not delectable. Throughout the course of illness, serum level of nitrate did not increase as determined by Sievers Nitric Oxide Analyzer. Analysis of HLA typing revealed these patients all negative for HLA-B53 and HLA-DRB1*1302. These results suggest that both NK cells CDS+ T cells may play important roles in the host defense mechanisms against acute uncomplicated malaria. zyxwvutsrqponmlkjihgfedcbaZYXW O-0531 SERUM LEVELS OF CYTOKINES AND RBCEPTORS IN MALARIA: AS!#XXATION WITH CEREBRAL MALARIA AND SEVERE MALARULANABMIA M, Department of Medical Zoology, Dokkyo University School of of Medicine, *tiesearch University in 15 lduIt of Parasitology, Gunma University School Institute of Medical Sciances, Tokai Akanmori BD’, Kurtzhals JAL”, G&a BQ”‘, Adabayeri V”‘. Oforl M’, Hvii L” zyxwvutsrqponmlkjihgfedcbaZYXWVU ’ lmmunolog~ Unit, Noguchi Memorial Institute for Medical Research, university of Ghana. Legon, Ghana. ** Centre for Medical Parasitology, University of Copenhagen, Denmark. *” Dept. of Child Health, University of Ghana Medical School, Korle-Bu, Ghana. Pfasmodium coatneyi-infected Japanese macaques (Macaws *ata) show severe clinical signs such as restlessness, dark- colored urine, shivering, dyspnea, cyanosis and anemia, and they are useful models to analyze the pathoganesis We examined kinetics of hematdogical of severe malaria. features, especially lymphocyte subsets, in two Japanese macaques and ona rhesus monkey (Maraca cop-infected mdatta)after intravenous inoculation with P. erythrocytes. The Japanese monkeys developed acute and fulminant infection with high parasitemia (4 1 or 3 1% each) and became moribund showing the typical clinical signs of severe malaria (12 or 14 days after inoculation). They showed decrease in T cell proportions of both CD4+ and CDB+ phenotypes when they were moribund. Specific antibody responses to the parasite were weak. Tha rhesus monkey, though suffered from severe anemia, did not show fulminant symptoms and finally recovered without any sequela. The proportion of CD20+ lymphocytes increased after 10 days post inoculation, which was accompanied by the increase of the parasite-specific antlbody titer. These differences in pro&s and immune response between the two species of monkeys will give us further understanding about the mechanism of severe malaria. Plasma levels of IL-IO, IL-4, IL-S, IL-12, IFN-y, TNF-a, TNF-RI, TNF-RII, IL-IRA, IL-2R. IL-IR, IL-6R. ICAM-1, E-s&&n and total IgE were measured for three strictly defined clinical categories of malaria in Ghanaian children, cerebral malaria (CM. n=41), seven malat+J anaemia (SA, n=lO) and uncomplicated malaria (UM, n=26f. during the acute phase and after recovery. The data revealed close associations between high levels of both IL-2R and TNF and CM but not SA or UM during acute illness. In addition, TNF-RI, TNF-RI1 and IL-IRA levels were higher for both SA and CM patients compared with uncomplicated malaria. IL-10 levels were significantly lower in SA than in the other two categories of malaria (CM & UM). There was no association between any of the other parameters and the clinical categories of malaria. Although some cytolcines and receptors may reflect inflammatory responses and hence overall severity of illness in malaria others may reflect pathological changes associated with specific categories of malaria. The implications of these tindings for further investigations will be fully discussed.