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Biomedical subjects

L H Faccioli

Publications and source records attributed to L H Faccioli.

35 records · Page 2Linked to original sources
PubMed1997

Cytokines in the modulation of eosinophilia.

In this review we discuss our recently results showing interleukin 5 (IL-5) involvement in eosinophil migration and in the maintenance of eosinophilia in blood, bone marrow, lung and peritoneal cavity, in a visceral larva migrans syndrome model using guinea-pigs infected with Toxocara canis. We also describe the sequential release of TNF-alpha and IL-8 during the course of infection. Finally we propose a biological role for IL-5, at least in our model, as a modulator of IL-8 release and secretion.

Animals↗
PubMed1997

Participation of interleukin-5, interleukin-8 and leukotriene B4 in eosinophil accumulation in two different experimental models.

There are several experimental models describing in vivo eosinophil (EO) migration, including ip injection of a large volume of saline (SAL) or Sephadex beads (SEP). The aim of this study was to investigate the mechanisms involved in the EO migration in these two models. Two consecutive injections of SAL given 48 hr apart, induced a selective recruitment of EO into peritoneal cavity of rats, which peaked 48 hr after the last injection. SEP, when injected ip, promoted EO accumulation in rats. The phenomenon was dose-related and peaked 48 hr after SEP injection. To investigate the mediators involved in this process we showed that BW A4C, MK 886 and dexamethasone (DXA) inhibited the EO migration induced by SAL and SEP. To investigate the source of the EO chemotactic factor we showed that mast cells, macrophages (MO), but not lymphocytes, incubated in vitro in presence of SAL released a factor which induced EO migration. With SEP, only mast cells release a factor that induced EO migration, which was inhibited by BW A4c, MK 886 and DXA. Furthermore, the chemotactic activity of SAL-stimulated mast cells was inhibited by antisera against IL-5 and IL-8 (interleukins). SAL-stimulated MO were only inhibited by anti-IL-8 antibodies as well SEP-stimulated mast cells. These results suggest that the EO migration induced by SAL may be dependent on resident mast cells and MO and mediated by LTB4, IL-5 and IL-8. SEP-induced EO migration was dependent on mast cells and may be mediated by LTB4 and IL-8. Furthermore, IL-5 and IL-8 induced EO migration, which was also dependent on resident cells and mediated by LTB4. In conclusion, EO migration induced by SAL is dependent on mast cells and MO, whereas that induced by SEP is dependent on mast cells alone. Stimulated mast cells release LTB4, IL-5 and IL-8 while MO release LTB4 and IL-8. The IL-5 and IL-8 release by the SAL or SEP-stimulated resident cells may act in an autocrine fashion, thus potentiating LTB4 release.

Analysis of Variance↗
PubMed1996

Participation of interleukin-5 and interleukin-8 in the eosinophil migration induced by a large volume of saline.

Recently we demonstrated that the eosinophil migration into rat peritoneal cavities induced by a large volume of saline is mediated by LTB4 released by the resident macrophages and mast cells. In the present study, we have investigated the involvement of IL-5 and IL-8 in this process. We observed that saline-stimulated mast cells released the eosinophil chemotactic cytokines IL-5 and IL-8, while macrophages released only IL-8. These observations were confirmed by the ability of antibodies against IL-5 and IL-8 block the eosinophil chemotactic activity of the mast cell supernatants while the chemotactic activity of the macrophage supernatants was inhibited only by the antibody to IL-8. Recombinant forms of IL-5 and IL-8, when injected intraperitoneally, induced a dose-dependent eosinophil accumulation in naïve rats. The mechanism by which these cytokines induce eosinophil migration seems to be dependent on the resident cell population since depleting the peritoneal cavities of the latter renders the animals unresponsive to the eosinophil recruitment when challenged with IL-5, IL-8 or the supernatants of saline-treated mast cells or macrophages. Dexamethasone and MK 886 blocked the eosinophil migration induced by both the supernatants of saline-stimulated mast cells or macrophages and by IL-5 or IL-8. The IL-5-induced eosinophil migration was also blocked by BW A4C, another lipoxygenase inhibitor. Together, these results suggest LTB4 to be the lipoxygenase metabolite involved in the eosinophil recruitment induced by IL-5 and IL-8. Our results indicate that the eosinophil migration induced by saline is a complex phenomenon which is dependent on the resident mast cells and macrophages and is mediated by LTB4, IL-5 and IL-8. Mast cells release LTB4, IL-5 and IL-8, whereas macrophages release mainly LTB4 and IL-8. The inhibition of one of these mediators (IL-5, IL-8 or LTB4) completely blocked the eosinophil migration induced by saline, suggesting that they act synergistically.

Animals↗
PubMed1995

Differential correlation between interleukin patterns in disseminated and chronic human paracoccidioidomycosis.

In an attempt to understand better the immunoregulatory disorders in paracoccidioidomycosis (PCM), the possible correlation between interleukin pattern, lymphoproliferation, C-reactive protein (CRP) and specific antibody levels was investigated in the polarized clinical forms of this disease. We studied 16 PCM patients, eight with the disseminated disease (four under treatment and four non-treated) and eight with the chronic disease. The patients with disseminated disease exhibited high antibody titres specific to Paracoccidioides brasiliensis antigen compared with patients with the chronic form of disease. Tumour necrosis factor (TNF), IL-1, IL-6 and CRP in the serum of non-treated disseminated PCM patients were increased, which correlated positively with the low mitogenic response of peripheral blood mononuclear cells (PBMC) to phytohaemagglutinin (PHA) (P < 0.01) and with the high antibody titres (P < 0.001) of these patients. Moreover, we found in the disseminated PCM patients positive correlations between IL-1 and IL-6 (P = 0.0007); IL-1 and TNF (P = 0.0045); IL-1 and IL-6 with the high antibody titres (P = 0.0834 and P = 0.0631, respectively); IL-1, IL-6 and TNF with CRP levels. By contrast, no correlations were found with those interleukins in the treated disseminated and chronic patients or in controls. It was interesting to find an inverse correlation between IL-4 and antibody production in non-treated disseminated PCM (r = -0.4770); moreover, a significant correlation (P = 0.0820) was found in chronic PCM patients with respect to the low level of either IL-4 and antibody titres against fungus antigen. Chronic PCM patients also had IL-2 levels inversely correlated with antibody production (r = -0.6313; P = 0.0628). Inverse correlations were also observed between IL-2 and IL-6 levels in non-treated disseminated patients (P = 0.0501) and between IL-2 and IL-4 in chronic patients (P = 0.0131). The inflammatory cytokines might have a pivotal role in the genesis and in control of some aspects of the disease, such as granulomatous reaction, hypergammaglobulinaemia and depression of T cell-mediated immunity in PCM.

Adult↗
PubMed1995

LPS-induced 111In-eosinophil accumulation in guinea-pig skin: evidence for a role for TNF-alpha.

Lipopolysaccharide (LPS) is a major component of the cell wall of Gram-negative bacteria with powerful pro-inflammatory activities. Although the mechanisms involved in LPS-induced neutrophil accumulation have been studied extensively, few reports have focused on the effects of LPS on eosinophil infiltration. In this study we have used an in vivo model of local 111In-eosinophil accumulation in the guinea-pig to investigate the mechanisms of LPS-induced eosinophilia. Using a 4-hr in vivo test period, the intradermal injection of LPS (50-1000 ng/site) led to a marked and dose-dependent accumulation of 111In-eosinophils into guinea-pig skin sites. Time-course experiments revealed that this cell infiltration was delayed in onset, becoming significant 1 hr after the intradermal administration of LPS. The slow development of the response and its sensitivity to the locally administered protein synthesis inhibitor, actinomycin D, suggested that the LPS-induced 111In-eosinophil accumulation in vivo is mediated by the generation of de novo proteins. The intravenous pretreatment of guinea-pigs with a soluble tumour necrosis factor-alpha (TNF-alpha) receptor fusion protein (TNFR-IgG, 1 mg/kg), potently inhibited the 111In-eosinophil accumulation induced by LPS. Our results demonstrate that LPS can induce 111In-eosinophil accumulation in vivo in guinea-pig skin, and that this process is mediated by TNF-alpha.

Animals↗
PubMed1994

Investigation of the endogenous chemoattractants involved in 111In-eosinophil accumulation in passive cutaneous anaphylactic reactions in the guinea-pig.

1. Eosinophil accumulation and plasma extravasation are features of type I allergic responses. In an attempt to characterize the mediators of these responses, we have examined the local accumulation of 111In-eosinophils and leakage of 125I-human serum albumin (125I-HSA) during passive cutaneous anaphylaxis (PCA) reactions and in response to defined inflammatory mediators in the guinea-pig. Animals were passively sensitized by intradermal injection of anti-bovine gamma globulin antibody (50 microliters, 1/50 dilution). After 20-24 h, animals were injected intravenously with 111In-eosinophils and 125I-HSA for the measurement of cell accumulation and plasma leakage, respectively. 2. When injected into sensitized sites, antigen caused a dose-related increase in the accumulation of 111In-eosinophils and plasma leakage in guinea-pig skin. Time course experiments over 24 h revealed that the maximal rate of 111In-eosinophil accumulation occurred over the first 90 min, with little accumulation at later time points. Plasma leakage was completed within the first 30 min after challenge. Responses to the mast cell degranulator, compound 48/80, exhibited very similar responses to the PCA reaction. 3. Co-injection of antigen with the PAF antagonist, WEB 2086 (10(-7) mol/site) or the 5-lipoxygenase inhibitor, PF 5901 (10(-7) mol/site) did not significantly alter the accumulation of 111In-eosinophils or plasma leakage, whereas these drug doses abolished responses to exogenous PAF (10(-9) mol/site) and arachidonic acid (AA, 3 x 10(-8) mol/site), respectively. The H1 receptor antagonist chlorpheniramine (2.5 x 10(-8) mol/site) did not reduce antigen-induced 111In-eosinophil accumulation. Drug combinations were also injected with antigen into sensitized sites, but were unable to reduce "'In-eosinophil accumulation.4. These results indicate that anaphylactic eosinophil accumulation in this model involves mediators other than histamine, PAF or lipoxygenase products. This is in contrast to plasma leakage in this reaction, which can be abolished by a combination of antagonists blocking these mediators.

Animals↗
PubMed1994

Role of resident peritoneal cells in eosinophil migration induced by saline.

In the present study, we investigated the role of resident peritoneal cells as well as the mediators involved in the eosinophil migration induced by large volumes of physiological saline. Two consecutive intraperitoneal injections of saline given 48 h apart, induced a selective recruitment of eosinophils into the cavity. This response was not observed with phosphate-buffered saline (PBS). Saline-induced eosinophil migration may be mediated at least in part by LTB4, since the lipoxygenase inhibitors BW A4C and MK 886 prevented the response. In the presence of saline, but not of PBS, mast cells and macrophages incubated in vitro released a factor which induced eosinophil migration when injected into the peritoneal cavity of rats. This release was inhibited by BW A4C and MK 886. These results indicate the importance of mast cells and macrophages in the eosinophil migration induced by saline and suggest the participation of LTB4 in this phenomenon. An abrupt reduction in the extracellular potassium concentration at the membrane of resident cells may be responsible for the saline effects since addition of potassium ions to saline abolished the eosinophil chemotactic activity of the same as well as its ability to stimulate the release of eosinophil chemotactic factor in vitro. Dexamethasone blocked both the saline-induced eosinophil migration and the release of eosinophil chemotactic factor by mast cells and macrophages. Pretreatment of the animals with dexamethasone inhibited the eosinophil migration induced either by the supernatants of saline-stimulated mast cells and macrophages or by LTB4. These results indicate that the release of additional mediators is necessary in order to account for the final eosinophil migration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Eosinophil accumulation induced by human interleukin-8 in the guinea-pig in vivo.

Interleukin-8 (IL-8) is a neutrophil chemoattractant cytokine. Initially IL-8 appeared to exhibit specificity for neutrophils over other cells of the immune system. However, several recent studies have shown that this mediator can also activate other leucocyte types in vitro. In this study we have used an in vivo model of local [111In]leucocyte accumulation in the guinea-pig and an in vitro assay of leucocyte activation (changes in cytosolic-free Ca2+) to investigate the eosinophil chemoattractant activity of IL-8. The intradermal injection of recombinant human (rh)IL-8 induced a dose-dependent accumulation of intravenously administered [111In]eosinophils into the skin sites over 4 hr. Time-course experiments revealed that this cell infiltration was delayed in onset, occurring between 1 and 2 hr after injection of IL-8. The delay may indicate that IL-8 operates via an indirect mechanism. In contrast, eosinophil accumulation induced by the complement fragment C5a occurred within the first hour following injection. Other human cytokines, IL-1, IL-3, IL-5, tumour necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), were not eosinophil chemoattractants in this in vivo test system. Direct activation of eosinophils by IL-8 was demonstrated in vitro by a transient elevation in cytoplasmic-free Ca2+ levels where it was less potent than either rhC5a or leukotriene B4 (LTB4). Experiments using [111In]neutrophils in vivo indicated that rhIL-8 and rhC5a were similar in potency in inducing local neutrophil infiltration into guinea-pig skin. The demonstration of the eosinophil chemoattractant activity of IL-8 in vivo raises the possibility that this cytokine, or a structurally related molecule, contributes towards eosinophil infiltration in a number of inflammatory conditions such as asthma, helminthic infections and adult respiratory distress syndrome.

Animals↗
PubMed1992

Blockade of hyperalgesia and neurogenic oedema by topical application of nitroglycerin.

Surprisingly, a single topical application of a nitroglycerin (NTG) gel in humans has been shown to cause analgesia and to reduce oedema in thrombophlebitis. In the present investigation, we showed that the NTG gel reduces prostaglandin E2-induced hyperalgesia and blocks neurogenic inflammation induced in rat skin by antidromic electrical stimulation of the saphenous nerve. These results offer an explanation for the effects of topical application of NTG observed in thrombophlebitis, which may be common to other cutaneous pathologies. The data also support the development of nitrates the effects of which are restricted to the site of application.

Administration, Topical↗
PubMed1992

Tumor necrosis factor and macrophage activation are important in clearance of Nocardia brasiliensis from the livers and spleens of mice.

The roles of tumor necrosis factor (TNF) and macrophage activation in clearance of Nocardia brasiliensis from BALB/c mouse livers and spleens were evaluated. TNF activity was detectable in sera from animals at all stages of infection. Treatment of infected mice with an antiserum against TNF significantly enhanced the experimental infection as judged by enumeration of CFU in the spleens and livers of infected mice. In another set of experiments, a population of activated macrophages from the peritoneal cavities of N. brasiliensis-infected mice was studied by using a cytostatic assay. The observed cytotoxic activity of these activated macrophages against L929 cells was mediated by TNF, since this activity was inhibited by anti-TNF antiserum treatment. The level of TNF activity generated in vitro in the presence of lipopolysaccharide (LPS) by peritoneal macrophages from infected mice was higher than that of adherent peritoneal cells obtained from normal mice after challenge with LPS. When the nocardiacidal activity of peritoneal cells from N. brasiliensis-infected mice was estimated in vitro, a significant decrease in the number of CFU recovered was observed. Moreover, nocardiacidal activity of peritoneal cells obtained from N. brasiliensis-infected mice previously treated with anti-TNF antiserum was significantly reduced compared with the activity of cells obtained from infected mice previously treated with normal rabbit serum and that of cells from uninfected mice. These data suggest a role for TNF in resistance to N. brasiliensis infection.

Animals↗
PubMed1991

The accumulation of 111In-eosinophils induced by inflammatory mediators, in vivo.

Eosinophils are implicated in the pathogenesis of a variety of allergic inflammatory diseases such as asthma. Several substances have been shown to be chemotactic for eosinophils in vitro, but the inflammatory mediators involved in the accumulation of eosinophils in vivo are as yet unidentified. In this study we have developed a system to measure the accumulation of 111In-eosinophils in guinea-pig skin in vivo. Horse serum-induced guinea-pig peritoneal eosinophils were radiolabelled with 111In and injected intravenously into recipient animals. 125I-albumin was also injected intravenously in order to measure local oedema formation simultaneously. A range of putative mediators was injected intradermally and responses measured for up to 2 hr. Of the mediators tested, guinea-pig C5a des Arg in zymosan-activated plasma was the most active. Recombinant human C5a (rHC5a) was also highly active, but less than the guinea-pig material. C5a des Arg in maximally activated plasma induced a 1500% increase in eosinophil accumulation, while rHC5a (10(-10) mol dose) induced a 600% increase. Platelet-activating factor (PAF) and leukotriene B4 (LTB4) were also tested for comparison. With respect to 111In-eosinophil accumulation, the order of potency of the mediators tested was as follows: guinea-pig C5a des Arg greater than LTB4 greater than PAF. In contrast, the order of potency of the mediators with respect to oedema formation was: PAF greater than guinea-pig C5a des Arg greater than LTB4. The techniques described will facilitate analysis of the mechanisms involved in eosinophil accumulation in defined inflammatory reactions.

Albumins↗
PubMed1990

Recombinant interleukin-1 and tumor necrosis factor induce neutrophil migration "in vivo" by indirect mechanisms.

The alpha and beta forms of recombinant interleukin-1 (IL-1 alpha and IL-1 beta) and of recombinant Tumor Necrosis Factor (TNF alpha and TNF beta) induced dose-dependent neutrophil migration into rat peritoneal cavities. Migration induced by both IL-1s showed a bell-shaped dose-response curve and IL-1 beta was 3-fold more potent than IL-1 alpha. Pretreatment of the animals with dexamethasone or depletion of the peritoneal macrophage population, abolished the neutrophil migration induced by the four cytokines. "In vitro" stimulation of macrophage monolayers with IL-1 beta and the TNFs released a factor into the supernatant which, unlike these cytokines, induced neutrophil migration in dexamethasone pretreated animals. These results suggest that the neutrophil migration induced by IL-1 alpha, IL-1 beta, TNF alpha and TNF beta is not due to a direct effect on neutrophils, but occurs via the release of a chemotactic factor(s) from resident macrophages.

Animals↗
PubMed1988

Mouse cachexia induced by trehalose dimycolate from Nocardia asteroides.

Trehalose dimycolate (TDM) isolated from Nocardia asteroides induced in mice a severely wasted condition known as cachexia. Intraperitoneal injection of mice with five 10 micrograms doses of TDM in mineral oil at intervals of 2 d killed 90% of the animals within 26 d. Death followed a precipitous weight loss and an inflammatory process in the peritoneal cavity. When mice were injected intraperitoneally with a single 10 micrograms dose of TDM, 48 h later, they had begun to lose weight and exhibited extreme hypertriglyceridaemia and hypoglycaemia. Tumour necrosis factor (or cachectin) was detected in the plasma from animals injected with TDM. This cytokine released by mononuclear phagocytes may be involved in the induction of cachexia by TDM.

Animals↗
PubMed1988

Tumor necrosis factor (cachectin) mediates induction of cachexia by cord factor from mycobacteria.

The mechanism by which cord factor (CF), a toxic glycolipid from mycobacteria, induces cachexia was studied in BALB/c mice. Body weight was markedly reduced 48 h after CF administration; the animals became severely wasted and exhibited hypertriglyceridemia, hypoglycemia, and high levels of tumor necrosis factor (TNF) in plasma. After CF administration, a transferable factor which caused cachexia and hypertriglyceridemia in recipient mice was detected in the blood. Dexamethasone partially inhibited the cachexia-inducing action of CF. Conditioned medium from adherent peritoneal cell cultures incubated with CF produced the same wasting symptoms when inoculated intravenously into mice. These studies also demonstrated that adherent peritoneal cells produced a humoral factor in response to CF which was related to CF-induced cachexia. Antiserum to recombinant TNF-alpha prevented the cachectin action in passive-transfer experiments. Our findings indicate that cachectin (TNF) plays a role as a central mediator of the wasting induced by CF.

Animals↗
PubMed1988

The role of cachectin/TNF in the pathogenesis of tuberculosis.

The presence of cachectin or tumor necrosis factor (TNF) associated with hypertriglyceridemia was demonstrated in the serum of patients with pulmonary tuberculosis. The hyperlipidemia that accompanies this infection may be mediated by the TNF inhibition of lipoprotein lipase activity. This sequence of events may be sufficient to explain, in part, the complex metabolic changes and emaciation observed in tuberculosis patients.

Adolescent↗
PubMed1985

The anti-oedematogenic effect of SRS as an additional factor in the mode of action of non-steroid anti-inflammatory drugs.

A partially purified preparation of SRS was obtained from peritoneal exudates induced by a non-anaphylactic immediate hypersensitivity reaction. This preparation injected in the rat skin caused vasoconstriction and when administered together with carrageenin reduced oedema formation. Injection of carrageenin into the peritoneal cavity progressively increased exudate formation. Pretreatment of the animals with anti-inflammatory doses of aspirin, indomethacin and salicylate significantly reduced exudate formation and this inhibition was correlated with the appearance of SRS in the exudates. It is suggested that, in some inflammatory exudates, stimulation of the synthesis of vasoconstrictor SRS might be an additional factor to the inhibition of prostaglandin synthesis induced by non-steroid anti-inflammatory drugs.

Animals↗