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Resume Le paradoxe de l'infection retrovirale reside dans le fait qu'elle induit une hyperactivation du systeme immunitaire conduisant a une reponse immunitaire inefficace. Dans ce contexte, le reseau des cytokines, qui jouent un role fondamental dans la regulation du systeme immunitaire, est fortement sollicite. Une modification du profil des cytokines, resultant de la deregulation de ce systeme par l'infection virale, peut etre associee a la progression de la maladie; et les cytokines peuvent etre impliquees dans le processus de replication virale. Des cytokines, des inhibiteurs de cytokines ainsi que des mediateurs cellulaires anti-VIH sont a la base de strategies d'immunotherapie. Cette revue analyse l'implication des cytokines dans l'hyperactivation du systeme immunitaire induite par VIH-1, les consequences sur le desequilibre du profil cytakinique et le deficit des cellules T, ainsi que l'implication des cytokines dans les troubles hematologiques et oncogenes lies au VIH-1. Le potentiel diagnostique et pronostique lie a la detection des cytokines ainsi que leur importance dans les strategies d'immuno-intervention sont discutes.

Resume Une complication possible consecutive a l'implantation de protheses a base d'hydroxyapatite (HA) est la liberation de particules d'usure etant susceptibles d'induire une reaction inflammatoire sur le site d'implantation apres phagocytose de ces particules par des monocytes. Il a ete precedemment montre qu'en utilisant un rapport surfacique de 1 pour 1 (surface particules–surface cellules) certaines particules d'HA induisaient l'expression et la production de cytokines impliquees lors d'une reaction inflammatoire. Dans cette presente etude, nous avons etudie l'effet d'un rapport surfacique de 10 pour 1 sur la synthese de cytokines (TNF-α, IL-6, IL-8 et IL-10) produites par des monocytes humains en reponse a des particules d'HA de differentes formes. Nous avons mis en evidence que l'expression des cytokines augmentait avec le rapport surfacique alors que la production etait regulee et ce, semble-t-il, de facon post-transcriptionnelle.

Cytokine synthesis and secretion by blood mononuclear cells is a well-documented phenomenon in hemodialyzed patients. The present study was conducted in 17 chronically hemodialyzed patients to test the relative effect of uremic toxicity, membrane biocompatibility, dialysate composition, and the risk of endotoxinemia on the serum level of tumor necrosis factor-alpha (TNF-alpha). The only significant parameter that influenced circulating TNF-alpha was the chemical characteristics of the dialyzer membrane. Tumor necrosis factor-alpha levels significantly increased during the session with cuprophane, whereas they decreased with AN69. The TNF-alpha increase was documented whatever the dialysate buffer and the presence or absence (negative Limulus amoebocyte lysate test) of endotoxin in the dialysate. In the subgroup of patients treated with a contaminated dialysate and AN69, none had clinical symptoms and the central body temperature remained constant throughout the session. In these patients, serum TNF-alpha levels did not change after priming the dialyzer with sterile saline. In conclusion, the serum TNF-alpha level during hemodialysis appears to be modulated by biocompatibility, permeability, and binding properties of dialysis membrane rather than dialysate composition. Endotoxin in the dialysate did not result in positive TNF-alpha balance no matter what its possible priming effect on mononucleated blood cells.

Summary RU-41740, a glycoprotein extract from Klebsiella pneumoniae K2O1 strain, is an immunomodulating compound which has been shown to reduce infectious episodes in immunodeficient patients. Data from preliminary experimental designs suggested that RU-41740 could affect several target cells, such as T cells, B cells and macrophages. In the present report, we show that RU-41740 is a selective B-lymphocyte activator. It induces blast transformation in Nude mouse spleen cell cultures and in B-cell-enriched fractions obtained from normal mice. It does not activate T lymphocytes to proliferate. Activation of mouse B lymphocytes by RU-41740 is not affected by removal of adherent cells. RU-41740 also activates immunoglobulin secrection by murine B lymphocytes. Incubating spleen cells from C3H/HeJ mice with RU-41740 results in cell proliferation and activation of antibody-forming cells. This suggests that B-cell activation is not due to LPS contamination. Other experiments show that RU-41740 can also trigger mouse macrophages to produce interleukin-1 activity. Indeed, supernatants from peritoneal adherent cells incubated in the presence of RU-41740 can stimulate blastogenesis in thymocytes from C3H/HeJ mice. Thus, B-cell activation and IL-1 production by macrophages could constitute two additive mechanisms involved in immunomodulation induced by RU-41740.

RU-41740, a glycoprotein extract from Klebsiella pneumoniae, is an immunomodulating agent with a broad spectrum of activities. It enhances several macrophage functions, including interleukin-1 (IL-1) secretion. Present data show that RU-41740 was able to promote murine macrophage cytotoxicity against tumour cells. A soluble cytotoxic factor (CF) was found in supernatants from macrophage cultures stimulated with RU-41740. These supernatants were shown to contain IL-1. CF was detected on L-929 cells sensitized by actinomycin D. CF was analysed on the basis of MW and pHi: after gel filtration on "Ultrogel Aca54", a single peak of CF was found in the range of 50-60 Kd and was then distinct from IL-1, which was eluted at 15 Kd. After chromatofocusing, CF was found in a narrow peak of pH 4.8. CF was detected in supernatants 2 h after macrophage stimulation by RU-41740, and its release was abolished by pretreatment of macrophages with cycloheximide (2 micrograms/ml). CF described here shares several properties with tumour necrosis factor (TNF).

Resume Les auteurs rapportent le cas d'une septicemie a Yersinia enterocolitica survenue chez un diabetique dont l'hospitalisation a permis de decouvrir un deficit en glucose 6 phosphate deshydrogenase (G 6 PD) et une double hemoglobinopathie S-C. Malgre un terrain deficient, la guerison a ete obtenue grâce a l'antibiotherapie. Le germe, isole du sang du malade, n'a pas ete retrouve dans les selles. La souche a ete inoculee a des souris normales et a des souris athymiques (Nude). Elle n'a ete retrouvee qu'au niveau des organes des souris athymiques, hormis le contenu intestinal.

The concanavalin A-unreactive variants of alpha 1-acid glycoprotein introduced in culture medium of monocytes/macrophages induces the inhibition of thymocyte proliferative activity of interleukin 1. LPS or LPS receptors were not involved in the activity of alpha 1-acid glycoprotein on macrophages. alpha 1-acid glycoprotein did not show any direct effect on thymocytes whereas the monocyte/macrophage-supernatant inhibited the interleukin 1 proliferative effect. The activity of tumor necrosis factor and interleukin 2 was not altered by the alpha 1-acid glycoprotein-macrophage supernatant.

Resume Cette revue generale concerne la phagocytose ; notamment les mecanismes bactericides et les methodes permettant leurs explorations. Les differentes etapes impliquees dans la phagocytose et la bactericidie sont les suivantes : chimiotactisme, opsonisation, contact cellulaire, ingestion et digestion. L'adhesion fait intervenir les recepteurs specifiques de membrane (fragment Fc des IgG et la fraction C 3 du complement) ainsi que des facteurs extra-cellulaires. Apres la description de l'internalisation, les aspects morphologiques et physiologiques de la bactericidie sont decrits. Des modifications metabolique interviennent durant l'ingestion et la digestion. Ces activites bactericides peuvent etre separees en deux classes qui sont : -- soit oxygene independantes, -- soit oxygene dependantes. Dans la 1 re classe, on distingue les mecanismes enzymatiques impliquant le lysozyme et ceux, non enzymatiques, utilisant la lactoferrine et les proteines cationiques. Differents facteurs participent au second systeme. Des complexes letaux peuvent etre generes par oxydation des halogenes. De plus, d'autres composants sont aussi impliques comme l'eau oxygenee (H 2 O 2 ), les anions superoxyde (O 2 ), les radicaux hydroxyls et le singlet oxygene ( 1 0 2 ). Ils necessitent l'intervention de la NADPH, H + oxydase et de la superoxyde dismutase. L'etude de l'activite bactericide intra-cellulaire s'effectue : -- soit par l'evaluation des bacteries ingerees, -- soit par la mesure des modifications metaboliques : consommation d'oxygene, production de H 2 O 2 , generation de (O − 2 ) et de O 2 et augmentation de diverses activites enzymatiques (NADPH, H + oxydase, superoxide dismutase, myeloperoxydase). Cependant, notons que chacune de ces methodes n'explore seulement qu'un des nombreux mecanismes bactericides.

RU-41740, a glycoprotein complex extracted from Klebsiella pneumoniae, is an immunomodulating agent which acts on B cells and macrophages. It has been shown that RU-41740 is composed mainly of two macromolecular fractions, F1, having an LPS-related structure, and P1, with a proteoglycan structure. In the present paper, the effects of these molecules on B cells and on IL-1 and tumour necrosis factor (TNF), production by macrophages were compared. Data reveal that both fractions were mitogenic for murine B cells and induced IL-1 and TNF production by macrophages. The LPS-like fraction (F1) was sensitive to polymyxin B and was unable to activate macrophages and spleen cells from LPS non-responder mice. The P1 fraction was mitogenic for B cells and induced the production of IL-1 and TNF activities by macrophages from LPS non-responder C3H/HeJ mice. The cytotoxic activity was due to TNF alpha, since treatment with anti-TNF alpha antiserum abrogated the lytic activity of supernatants from stimulated macrophages. The differences observed between P1 and F1 fractions in terms of sensitivity to polymyxin B and activity towards C3H/HeJ spleen cells and macrophages suggest that the two structurally distinct molecules isolated from RU-41740 could act at different sites on immunocompetent cells.

Sodium periodate treatment of human peripheral blood lymphocytes at submitogenic concentrations (10 −4 M ) completely inhibits their ability to mount a primary in vitro antibody response to trinitrophenyl-polyacrylamide beads. Transfer experiments show that (i) mitogenic concentrations (2 × 10 −3 M ) of sodium periodate induce suppressor cells to the in vitro antibody response: (ii) the generation of these suppressor cells is decreased but not abolished after mitomycin treatment, whereas that of Con A-induced suppressors is prevented; (iii) the periodate-induced suppression is present in the T-enriched fraction; and (iv). upon periodate treatment, T-depleted cells have a moderate but significant suppressive effect.

Resume Une observation d'epidurite a Haemophilus aphrophilus est rapportee. Le diagnostic bacteriologique repose sur la mise en evidence de cette bacterie, a 3 reprises, a l'hemoculture. La guerison complete a ete obtenue par immobilisation et administration d'ampicilline et gentamicine.