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Biomedical subjects

M Sironi

Publications and source records attributed to M Sironi.

At least 163 records · Page 9Linked to original sources
PubMed1990

Intracerebroventricular injection of interleukin 1 induces high circulating levels of interleukin 6.

IL-1 is known to have a central role in the induction of acute-phase response, and some of its activities (including induction of some acute-phase proteins) were reported to be mediated by an induction of IL-6. Administration to rats of 200 ng of human rIL-1 by intracerebroventricular injection resulted in a more marked induction of circulating IL-6 than the same dose of IL-1 administered systemically (intravenously or intraperitoneally). Induction of serum IL-6 by centrally administered IL-1 was also observed in hypophysectomized or adrenalectomized rats, suggesting that activation of the hypothalamus-pituitary-adrenal axis is not essential for this effect of IL-1. IL-6 induction was also observed after pretreatment with indomethacin, indicating that the effect was dissociated from the pyrogenic activity of IL-1. Induction of IL-6 by a central action could represent a novel pathway in IL-1-induced acute-phase response.

Adrenalectomy↗
PubMed1990

3-Methylcholanthrene induces differential inhibition of humoral and cell mediated immune responses in mice of different ages.

C57B1/6 mice aged 2-3 and 13-14 months were treated i.p. with 3-methylcholanthrene. A single dose of 25 mg/kg reduced primary antibody production to the T-dependent antigen sheep red blood cells by 20% in mice aged 2-3 months and by 90% in 13-14-month-old animals. The same treatment did not reduce antibody production to the T-independent antigen pneumococcal polysaccharide type III in young mice, but reduced this response by 50% in 13-14-month-old animals. Blastogenesis to concanavalin A, phytohemagglutinin and alloantigens, that is mediated by T lymphocytes, was consistently reduced in young animals but only marginally affected, when at all, in 13-14-month-old mice. Blastogenesis to lipopolysaccharide, mediated by B lymphocytes, was reduced in mice of both ages, though in older mice it was affected later than in younger animals. Addition of 3-methylcholanthrene in vitro increased T lymphocyte responses equally in mice of both ages and did not modify B lymphocyte proliferation. Results presented here show that older mice are not necessarily more susceptible to all types of immunosuppression induced by a xenobiotic like 3-methylcholanthrene and that the sensitivity of the different facets of the immune response can change with aging.

Age Factors↗
PubMed1990

In vivo effects of cyclosporin A on murine B-cells responding to type III pneumococcal polysaccharide.

The effect of cyclosporin A (CSA) on the antibody response to pneumococcal polysaccharide type III (a T-independent class 2 antigen) was investigated in mice. A single oral CSA administration (50 mg/kg) was able to depress (40%) the primary antibody response evaluated as spleen plaque-forming cells. Repeated treatments (12-50 mg/kg x 5) resulted in a higher degree of inhibition (80%) of anti-SIII response. Both single and repeated CSA treatments were active only when administered concomitantly with or after immunization, whereas no effects were seen with drug pretreatment. Comparable inhibitions of anti-SIII response were observed in control and nude mice suggesting a direct effect of CSA on B-cells.

Administration, Oral↗
PubMed1990

Interleukin-6 gene expression and production induced in human monocytes by membrane proteoglycans from Klebsiella pneumoniae.

The present study was designed to investigate the effect of membrane proteoglycans (MPG) from Klebsiella pneumoniae on IL-6 production by human peripheral blood monocytes. Exposure in vitro to MPG induced release of IL-6 activity from human monocytes, as assessed by the 7TD1 hybridoma assay. MPG-induced hybridoma growth factor activity was blocked by anti-IL-6 antibodies. MPG induced expression in human monocytes of IL-6 mRNA transcripts as assessed by Northern blot analysis. Induction of IL-6 in mononuclear phagocytes may play a role in the immunomodulatory activity of MPG.

Bacterial Outer Membrane Proteins↗
PubMed1989

IL-1 and IL-6 release by tumor-associated macrophages from human ovarian carcinoma.

Our study was designed to investigate the production of interleukin-1 (IL-1) and IL-6 in tumor-associated macrophages (TAM) isolated from ascites (18 cases) or solid (7 cases) human ovarian carcinoma. These are pleiotropic monokines which, in addition to affecting proliferation and differentiation of lymphocytes, act on various targets, including vascular cells and liver, and may therefore be involved in the pathogenesis of certain manifestations of malignancy. IL-1 was measured by the thymocyte co-stimulator assay, under conditions in which IL-6 was inactive, and, in 8 cases, by radioimmunoassay (RIA). IL-6 was measured as hybridoma growth factor (HGF) on the 7TD1 cell line. TAM did not release appreciable levels of IL-1 spontaneously and, upon LPS stimulation, were poor producers of this monokine compared to blood monocytes. In contrast, TAM supernatants contained a high level of HGF in the absence of deliberate stimulation, and exposure to LPS either did not affect or further augmented production of this monokine. HGF activity of TAM supernatants was completely blocked by anti-IL-6 antibodies. Ascites fluid from 8 ovarian-carcinoma patients contained high levels of HGF activity, blocked by anti-IL-6 antibodies. Thus, TAM exhibit a dissociation in their capacity to release the functionally related monokines IL-1 and IL-6. IL-6 produced by TAM may account for the elevation of liver-derived acute-phase proteins associated with malignancy.

Carcinoma↗
PubMed1989

IL-1 stimulates IL-6 production in endothelial cells.

Leukocytes and vascular cells interact closely in inflammation and immunity and lymphokines are important mediators of this interaction. The present study was designed to define the possible role of IL-6 as a communication signal between vascular and immunocompetent cells. IL-6 was measured as hybridoma growth factor (HGF) on the 7TD1 cell line in the supernatants of human endothelial cells (HEC). HEC released appreciable levels of HGF activity in the absence of deliberate stimulation. In vitro exposure to recombinant IL-1 beta markedly increased (usually 10 to 15-fold) HGF production by HEC. Optimal stimulation was observed with 0.1 to 50 U/ml for 4 to 20 h of incubation. Human and murine rIL-1 alpha stimulated HGF production in HEC. Anti-IL-6 antibodies inhibited the HGF activity of the HEC supernatants, thus confirming, together with the cytokine specificity of the assay, the nature of HEC-produced cytokine. IL-1-treated HEC expressed high levels of IL-6 mRNA as detected by Northern blot analysis. Inasmuch as IL-1 elicits a complex series of changes in HEC, it was important to assess whether IL-6, produced after exposure to IL-1, modified HEC function. Natural or rIL-6 did not affect the functional status of HEC as assessed by proliferative capacity, production of procoagulant activity and prostacyclin, ability to induce adhesion of polymorphonuclear leukocytes. The capacity to produce IL-6 may represent an important mechanism by which endothelial cells participate in inflammatory and immune reactions.

Blood Coagulation Factors↗
PubMed1989

Monokine production by microglial cell clones.

Cytokines have been suggested to act as intermediates between the immune and the central nervous system, but little is known about the type of cells synthesizing them in the brain. We have immortalized with oncogenic retroviruses primary brain cell cultures from mouse embryos and have generated clones of microglial cells that have been characterized. Three of the clones studied produce interleukin 1 (IL 1); IL 6 and tumor necrosis factor-alpha as assessed by biological assays and by Northern blot analysis. Our data raise the question on the role of these cytokines in the brain and suggest that early resident microglial cells might play an important role in development processes and in the adult brain.

Animals↗
PubMed1989

Morphometric evaluation of fine needle biopsy of single thyroid nodules.

Area, perimeter, maximum diameter and form factors of nuclei of FNABs of thyroid nodules were measured with a MOP Videoplan. 23 cases were selected from patients with a scintigraphically cold single thyroid nodule. The mean values of area, perimeter and maximum diameter were significantly different (p less than 0.001) between the adenoma and carcinoma cases; no differences were found for the form factors. Although the analyses gave significant results, a certain amount of overlap of the benign and malignant populations was present; therefore the significance of the standard deviation, assumed to be an index of variability of the nuclear area, was evaluated and this parameter was found to discriminate the two populations. The standard deviation of the nuclear area measured in 14 cases diagnosed as suspicious gave 77% accuracy in discriminating benign from malignant cases.

Adenoma↗
PubMed1989

Constitutive expression of the interleukin-6 gene in chronic lymphocytic leukemia.

Interleukin-6 (IL-6) is a pleiotropic lymphokine active as a growth factor on B-cell hybridomas and plasmacytomas and found to be identical with B-cell stimulatory factor 2, interferon beta 2, 26-Kd protein, and hepatocytes stimulating factor. IL-6 gene expression was investigated in fresh human chronic lymphocytic leukemia (B-CLL) and in acute lymphoblastic leukemia (ALL) by Northern blot analysis using a specific cDNA probe. 1.3-kb IL-6 transcript was found in six out of 11 B-CLL patients, while no hybridization was observed in ten cases of ALL of both T- and B-cell origin. The constitutive expression of IL-6 transcripts was associated with production of a biologically active protein as determined by using the IL-6-dependent 7TD1 cell line. It remains to be elucidated whether IL-6 gene expression is indeed important in the regulation of B-CLL growth or in its clinical manifestation.

Animals↗
PubMed1987

Effect of thymostimulin in models of cell-mediated and humoral autoreactivity and on T-dependent suppression.

To explore the therapeutic potential of the thymic hormone preparation thymostimulin (TS) in animal models of cell-mediated and humoral autoimmunity, its effects were investigated on experimental allergic encephalomyelitis in guinea pigs and on anti-erythrocytic autoantibody production in C57B1/6 mice. In both autoimmunity models, TS produced significant therapeutic effects in terms of proportion of diseased animals, disease severity and/or disease duration; however, both the TS dose and the time of treatment start relative to the disease-inducing stimulus critically influenced results. TS effects on the generation and expression of suppressive activity induced in C57B1/6 mice by a supraoptimal immunization with 10(10) SRBC were also examined. TS given after 10(10) SRBC did not influence the level of suppression, and the activity of effectors of suppression was not modified by this agent. Conversely, using a treatment protocol analogous to that effective in reducing murine autoantibody production, TS administration prior to 10(10) SRBC was associated with a significant increase in the subsequent generation of T-dependent, antigen-specific suppressive activity. These findings suggest that effects of TS on the development of suppressor cells may be involved in the activity of this agent in animal models of autoaggression.

Animals↗
PubMed1986

A preliminary analysis of the effects of elliptinium on immune reactivities in mice.

The immune effects of Elliptinium (2-methyl-9-hydroxyellipticinium, 9-HME), a chemical recently shown to possess clinical antineoplastic activity, were investigated in mice. Primary antibody responses to T-dependent and T-independent antigens, DTH reactivity and responsiveness to mitogens were significantly depressed only by post treatment with single drug doses of at least 5 mg/kg i.v., i.e. doses clearly above those known to exert full antitumoral effectiveness and to induce lymphoid cell depletion in the same species. Only drug doses in the LD50 range (i.e. 10 mg/kg) reduced the capacity of NK cells and of activated macrophages to express non-specific cytotoxicity towards tumor target cells. When repeated dose regimens were used, significant immune depression was again seen at doses above those displaying chemotherapeutic activity. Data obtained suggest that at chemotherapeutically effective dosages 9-HME possesses in mice a comparatively low immunodepressive potential and that immune cells mediating natural host defence mechanisms appear especially resistant to this drug.

Alkaloids↗
PubMed1986

Immunohistochemical study of the appearance of some markers in liver adjoining hepatocellular carcinoma.

The presence and distribution of AFP, AAT and HBsAg in peritumoral non-neoplastic hepatocytes (NNH) of 27 cases and, at the same time, in the neoplastic tissue of 37 liver cell carcinoma (HCC) were studied; AFP and HBsAg were more frequently found in NNH than in HCC cells; no differences were found for AAT. The presence of HBsAg also in normal liver without cirrhosis is probably best explained by its possible role in neoplastic transformation and by the inhibition of replication of the viruses AFP, considered to be expression of dedifferentiated cells, may possible be taken up by NNH for catabolic purposes.

Aged↗
PubMed1986

Duodenal somatostatinoma with psammoma bodies: an immunohistochemical and ultrastructural study.

We report a case of malignant somatostatinoma of the ampulla of Vater in a 38-year-old woman with diabetes and cholelithiasis. Immunohistochemistry showed that tumor cells contained only somatostatin and electron microscopy revealed D-type granules in their cytoplasm. Psammoma bodies were numerous and appeared to originate in the cytoplasm of somatostatin producing cells. A review of the literature reveals that somatostatinomas with psammoma bodies are found only in the duodenum and do not produce significant amounts of peptides other than somatostatin.

Adenoma, Islet Cell↗
PubMed1986

Nutritional status, function of the small intestine and jejunal morphology after total gastrectomy for carcinoma of the stomach.

We studied the nutritional status and the prevalence of malabsorption in 12 patients one to three years after total gastrectomy (TG) for gastric neoplasm. The Roux-en Y technique was used for reconstruction. A correct dietary regimen according to the recommended daily allowance was suggested and patients were seen quarterly on an out patient basis. The nutritional status was evaluated by measuring serum albumin levels, total iron binding capacity, cholinesterase, area muscular circumference, triceps skinfold and delayed hypersensitivity response. Work-up studies for the small intestine included: stool fat, D-xylose and glucose tolerance tests, Schilling test (phase II and III), serum iron levels, serum vitamin B12 levels and biopsy of the jejunum. Malnutrition, defined as the occurrence of two or more abnormal nutritional parameters, was observed in one patient; glucose and D-xylose tolerance tests were normal in all. A mild degree of steatorrhea was observed in four patients. The second phase of the Schilling test was abnormal in eight patients, but urinary excretion of vitamin B12 increased in three of four patients after use of antibiotics. Low serum vitamin B12 levels were common after the twentieth postoperative month. Serum iron levels were initially low and returned to normal six months after TG. All patients had normal jejunal histologic findings. These data indicate that malnutrition after TG is not common if an adequate dietary intake is maintained. Malabsorption, possibly due to bacterial overgrowth, is not a major clinical problem.

Aged↗
PubMed1985

Liver cell dysplasia and hepatocellular carcinoma: a histological and immunohistochemical study.

Liver cell dysplasia (LCD) was found in 28 (60%) of 47 patients with hepatocellular carcinoma (HCC); 22 (79%) of them had associated liver cirrhosis. LCD was more frequently observed in posthepatitic cirrhosis (82%) than in the other forms. Carcinoembryonic antigen (CEA), alpha-1-antitrypsin (AAT) and alpha-fetoprotein (AFP), as demonstrated by the peroxidase-antiperoxidase method, were similarly expressed both in normal and in dysplastic cells. Hepatitis B surface antigen was found in eight cases (17%), six of which were associated with LCD. HBsAg was rarely found in dysplastic cells and frequently displayed a peculiar perinuclear pattern. The possible preneoplastic role of LCD is stressed.

Adult↗
PubMed1984

Chemotherapy-increased antineoplastic effects of antibody-toxin conjugates.

A model, employing murine L1210 leukemia to which the artificial determinant TNP was bound in vitro and an anti-DNP antibody-ricin A-chain conjugate, was used to explore the in vivo therapeutic potential of combined immunotoxin-chemotherapy treatment. Under conditions in which immunotoxin and chemotherapy as single therapies had only marginal therapeutic activity, their combined use was markedly effective.

Animals↗