Serum VEGF and b-FGF profiles after tension-free or conventional hernioplasty.

Angiogenesis is strongly influenced by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), whose production is also regulated by interferon (IFN)-gamma and interleukin (IL)-10. The aim of this study was to evaluate the modifications of serum VEGF, b-FGF, IFN-gamma and IL-10 levels in patients with inguinal hernia undergoing hernioplasty with the Lichtenstein technique (LH) using polypropylene mesh or with Bassini open conventional inguinal hernia repair (BH). MATERIALS AND METHODS: Randomly, 16 patients underwent BH, and 16 were treated with the LH technique using polypropylene mesh. Blood samples were collected 24 h prior to surgery and then 6, 24, 48 and …

Effect of partially modified retro-inverso analogues derived from C-reactive protein on the induction of nitric oxide synthesis in peritoneal macrophages

The ability of three modified tetrapeptides, representing fragments of the C-reactive protein (CRP) sequence and stabilized in the first peptide bond by retro-inverso modification, to affect the secretion of nitric oxide (NO) was studied in macrophages of BALB/c mice. These tetrapeptides, resembling the aminoacid sequence of tuftsin (CRP I, H-gThr-(R,S)mLys-Pro-Leu-OH, ITF 1192; CRP II, H-gGly-(R, S)mLys-Pro-Arg-OH, ITF 1127; CRP III, H-gThr-(R,S)mLys-Pro-Gln-OH, ITF 1193), were able to induce NO synthesis by peritoneal macrophages in a dose-dependent manner; the most stimulating dose was 1000 ng ml−1 for CRP II and 100 ng ml−1 for CRP I and CRP III. NO synthesis was not strictly dependent …

Estrogen regulates cytokine production and apoptosis in PMA-differentiated, macrophage-like U937 cells

We have investigated the effects of sex steroids, estradiol (E2), and testosterone (T) on the synthesis of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) in phorbol-myristate-acetate (PMA)-differentiated human monoblastic U937 cells. The ability of both hormones to modulate the viability and programmed cell death of macrophage-like PMA-differentiated U937 cells was also inspected. E2 increased TNF-alpha synthesis, whereas T had no effect on the production of this cytokine. The combination of E2 and its antagonist tamoxifen or ICI-182,789 completely abolished the induction of TNF-alpha, while combination of T and its antagonist Casodex (CSDX) did not significantly affect …

Modulation of Nitric Oxide Production by Tetracyclines and Chemically Modified Tetracyclines

Chemically modified tetracyclines (CMTs) dose-dependently decreased inducible nitric oxide synthase (iNOS) and, consequently, nitric oxide (NO) formation by the lipopolysaccharide (LPS)-stimulated J774 line. The inhibitory effect was due to a specific reduction in the iNOS protein content in the cells, as attested by Western blot analysis and by the inhibition of iNOS mRNA accumulation. Furthermore, CMTs cause a dose-dependent increase in cell death in the J774 line mediated by the NO-independent apoptotic mechanism.

Cytokines and growth factors in wound drainage fluid from patients undergoing incisional hernia repair

Knowing the dynamics of growth factor and cytokine secretion within the site of a surgical operation is important, as they play a crucial role in the pathophysiology of wound healing and are a target for modifying the repair response. The aim of this study was to evaluate the production of several cytokines and growth factors in the drainage wound fluid from patients undergoing incisional hernia repair: namely, interleukin (IL)-6, IL-10, IL-1alpha, IL-1 ra, interferon-gamma, vascular endothelial growth factors and basic fibroblast growth factor. Ten female patients with abdominal midline incisional hernia undergoing surgical repair were included in this study. In all cases, a closed-suction…

The Acute Phase Response in Sicilian Patients with Boutonneuse Fever Admitted to Hospitals in Palermo, 1992–1997

Abstract Objectives : To study the modifications of some components of the acute phase response (APR) in Sicilian patients with boutonneuse fever (BF) caused by Rickettsia conorii . Methods : Sera from 500 Sicilian patients with confirmed BF were studied at the time of diagnosis and every week after treatment, and after recovery for the presence of various inflammatory mediators. Tumour necrosis factor α (TNFα), interleukin(IL)-6, IL-1α, IL-8, soluble TNF receptors (sTNF-R) and sIL-6R were assayed by commercially ELISA kits. C3, C4, factor B, C-reactive protein (CRP), fibrinogen, ceruloplasmin (Cp) and α 1 -antitrypsin (AAT) were assayed by a rate nephelometry. Results : Interferon gamma (I…

Tetracycline inhibits the nitric oxide synthase activity induced by endotoxin in cultured murine macrophages

Here we investigate the effects of tetracycline base and of a semi-synthetic tetracycline derivative, doxycycline, on the induction of inducible nitric oxide synthase and, hence, on the production of nitric oxide (NO) by lipopolysaccharide in J774 macrophage cultured in vitro. The treatment of J774 line with tetracycline base (6.25-250 microM) or doxycycline (5-50 microM) dose-dependently decreased the lipopolysaccharide-stimulated (1 microg/ml) inducible NO synthase activity and, consequently, nitrite formation. For instance, the inhibition was 70% for tetracycline base at 250 microM and 68% for doxycycline at 50 microM. The inhibitory effect of tetracyclines was due neither to a reduction…

Effects of chemically modified tetracyclines (CMTs) in sensitive, multidrug resistant and apoptosis resistant leukaemia cell lines

Recently discovered chemically modified tetracyclines (CMTs) have shown in vitro and in vivo anti-proliferative and anti-tumour activities. Here, we evaluated in vitro the anti-proliferative and apoptotic activity of six different dedimethylamino chemically modified tetracyclines (CMT-1, CMT-3, CMT-5, CMT-6, CMT-7 and CMT-8) in sensitive and multidrug resistant myeloid leukaemia cells (HL60 and HL60R) in vitro. Three of these compounds (CMT-5, CMT-6, CMT-7) showed low cytotoxic activity both in sensitive and in resistant cells, CMT-3 was endowed with a high anti-proliferative activity only in sensitive cells and was moderately effective as apoptosis inducing agent, with an activity similar …

Matrix metalloproteinases production in malignant pleural effusions after talc pleurodesis

SUMMARY In this study we have evaluated the modifications of matrix metalloproteinases (MMPs) in malignant pleural fluids taken from patients suffering from lung cancer and treated with intrapleural talc instillation to induce pleurodesis. Furthermore, we have analysed the variations of some inflammatory mediators (C-reactive protein, α-1 antitrypsin) and of a protein (plasminogen) involved in MMP activation. In all patients the clinical improvement after talc pleurodesis was followed by a reduction in MMP-1, TIMP-1, C-reactive protein, α-1 antitrypsin and plasminogen activity. Furthermore, MMP-9 levels were variable; in fact, in some patients they were high at the beginning of treatment, i…

Sex hormones modulate inflammatory mediators produced by macrophages.

CD4+ CCR5+ and CD4+ CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis

The potential involvement of apoptosis in the pathogenesis of visceral leishmaniasis (VL) was examined by studying spontaneous and Leishmania antigen (LAg)-induced apoptosis using cryopreserved peripheral blood mononuclear cells (PBMC) of Sicilian patients with VL. Results indicate that monocytes and T lymphocytes from acute VL patients show a significantly higher level of apoptosis compared with that observed in healed subjects. The percentage of apoptotic cells was higher in monocytes than in T lymphocytes. T cells involved in programmed cell death (PCD) were mainly of the CD4(+) phenotype. In particular, the T helper 1-type (Th1) subset, as evaluated by chemokine receptor-5 (CCR5) expres…

IL-15 in human visceral leishmaniasis caused byLeishmania infantum

SummaryInterleukin (IL)-15 is a recently discovered cytokine with the ability to stimulate the proliferation activity of Th1 and/or Th2 lymphocytes. Here, we investigated the involvement of IL-15 in the immune response to Leishmania infantum infection by studying patients with visceral leishmaniasis (VL). We found that IL-15 is produced by leishmanial antigen (LAg)-stimulated peripheral blood mononuclear cells (PBMC) from active VL patients at a significantly higher level than those produced by cells from healed VL subjects or healthy controls. A significant increase in IL-15 serum blood levels was also observed in acute VL patients compared with healed ones. Furthermore, recombinant IL-15 …

Prostaglandin E2 regulates inducible nitric oxide synthase in the murine macrophage cell line J774.

We have evaluated the role of prostaglandin E2 (PGE2) in the synthesis of nitric oxide (NO) by the activation of the inducible form of nitric oxide synthase (NOS) in the murine macrophage cell line, J774, stimulated with different doses of lipopolysaccharide (LPS). The stimulation of the J774 line with suboptimal doses of LPS (0.1 microgram/mL) caused a production of endogenous PGE2 that was capable of stimulating NOS activity inducing an increase in the NO synthesis, as attested by the fact that cyclooxygenase enzyme inhibitor, indomethacin, significantly reduced NO secretion. On the contrary, a higher dose of LPS (1 microgram/mL) produced high levels of PGE2 that reduced the levels of NOS…

Intraperitoneal injection of tetracyclines protects mice from lethal endotoxemia downregulating inducible nitric oxide synthase in various organs and cytokine and nitrate secretion in blood

We have tested whether tetracyclines (TETs) are able to protect mice from lipopolysaccharide (LPS)-induced shock, a cytokine-mediated inflammatory reaction. Mice, injected with a single dose of tetracycline base (TETb; 1.5, 10 and 20 mg/kg of body weight) or doxycycline (DOXY; 1.5 mg/kg), were significantly protected from a lethal intraperitoneal injection of LPS (500 micrograms per mouse). TETs acted in early events triggered in response to LSP; in fact, they were no longer significantly protective if injected more than 1 h after the injection of endotoxin. LPS-treated mice protected by TETs showed a significant inhibition of tumor necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL…

Modifications in the production of cytokines and growth factors in drainage fluids following mesh implantation after incisional hernia repair

Abstract Background The aim of this study was to evaluate changes in the production of some cytokines (interleukins [ILs]-6, -10, -1, and -1ra), vascular endothelial growth factor, and beta-fibroblast growth factor after polypropylene mesh implantation. Methods Twenty female patients were divided into 2 groups. In 1 group, hernia repair was performed with conventional sutures (CR), whereas in the other group polypropylene mesh (MR) was used. Growth factors and cytokines production was analyzed in wound drain fluids based on the amount produced during 24 hours. Results IL-1 increased substantially in MR patients on postoperative days 1 and 2. IL1-ra and IL-10 production was always significan…

Anti-inflammatory effects of chemically modified tetracyclines by the inhibition of nitric oxide and interleukin-12 synthesis in J774 cell line

We investigated the effects of chemically modified tetracyclines (CMTs) on the production of nitric oxide (NO) and on the synthesis of some cytokines: tumour necrosis factor alpha (TNF-alpha), interleukin(IL)-10 and IL-12 in lipopolysaccharide (LPS)-treated J774 cell line. Furthermore, we studied the ability of these drugs to modify the viability in LPS-stimulated J774 macrophages. CMTs decreased, in a dose-dependent manner, inducible NO synthase (iNOS) activity and, consequently, nitrite formation in J774 cultures. The CMT-induced decrease in NO production is due to the inhibition of enzyme activity rather than to a direct effect on enzyme expression. The absence of the inhibition in mRNA …

Chemically modified tetracyclines induce cytotoxic effects against J774 tumour cell line by activating the apoptotic pathway

Here, we have studied the effects of chemically modified tetracyclines (CMTs) on apoptosis both at the level of the cytoplasmic proteolytic caspase cascade, and on Bcl-2 and c-myc mRNA expression in the J774 macrophage cell line. The results indicate that CMTs induce morphological changes consistent with apoptotic events, as clearly demonstrated both by the acridine orange and ethidium bromide staining, and by TUNEL and fragmentation ELISA assays. Furthermore, the analysis of the cell cycle by flow cytometry shows an evident apoptotic sub-G0G1 peak, without important modifications in the cell cycle distribution. CMTs induce programmed cell death (PCD) in a dose-dependent manner and CMT-8 is…

Cytokine modifications after tension-free hernioplasty or open conventional inguinal hernia repair

Abstract Background: The purpose of this study was to evaluate the involvement of proinflammatory cytokines (interferon-γ [INF-γ], interleukin [IL]-6) and anti-inflammatory cytokines (IL-4, IL-l0, IL-13) in patients undergoing Lichtenstein tension-free hernioplasty (LH) using polypropylene prosthetic materials or conventional Bassini hernia (BH) repair. Methods: Thirty-five male patients (age range 25 to 60 years) with unilateral inguinal hernia without complications or recurrence were included in this study. Randomly, patients underwent conventional operation and had their inguinal hernia repair performed with polypropylene mesh. Peripheral venous blood samples were collected 24 hours prio…

Ex vivoevidence for PGE2and LTB4involvement in cutaneous leishmaniasis: relation with infection status and cytokine production

SUMMARYEx vivoculture of spleen cells from BALB/c mice infected with 2 × 106Leishmania major(L.major) promastigotes were cultured with ConcanavalinA (ConA) or leishmanial antigen (L. Ag) and tested for prostaglandin E2(PGE2) and for leukotriene B4(LTB4), in order to study their involvement in the evolution of cutaneous leishmaniasis and the connexion with lymphokine-mediated responses. The data were compared with those obtained in BALB/c mice protected againstL. majorby sublethal irradiation (550 rad; cured mice). In the unprotected BALB/c mice the levels of PGE2that were responsible for the depression of interferon-γ (IFN-γ) and tumour necrosis factor-α (TNFα) Th1-associated cytokines and …

Acute inflammatory response after inguinal and incisional hernia repair with implantation of polypropylene mesh of different size.

The purpose of this study was to assess the modifications of interleukin (IL)-6, C-reactive protein (CRP), leukocytes and fibrinogen after implantation of polypropylene mesh.Thirty-six patients were included in this study and divided into two groups. To the first group were allocated patients affected by inguinal hernia and undergoing conventional repair (subgroup Ia) or hernioplasty with 40-cm(2) polypropylene mesh (subgroup Ib). To the second group were allocated patients affected by incisional hernia and undergoing conventional repair (subgroup IIa) or incisional hernia repair with 400-cm(2) polypropylene mesh (subgroup IIb). Peripheral venous blood samples were collected 24 h before sur…

Interleukin-15, as Interferon-gamma, Induces the Killing of Leishmania infantum in Phorbol-Myristate-Acetate-Activated Macrophages Increasing Interleukin-12

The potential leishmanicidal activity of interleukin-15 (IL-15) was examined while priming with the cytokine phorbol-myristate-acetate (PMA)-activated macrophages and infecting them with Leishmania infantum parasites. The activation of macrophage cultures with IL-15 determined a significant anti-leishmanial activity, comparable with that induced by interferon-gamma (IFN-gamma). The killing of Leishmania in macrophages primed with IL-15, as well as with IFN-gamma, was followed by an increase in the IL-12 synthesis. The neutralization of IL-15 or IFN-gamma, by specific monoclonal antibodies (MoAb) caused a significant reduction in leishmanicidal activity. Furthermore, in PMA-activated macroph…

Anti-inflammatory effects of annexin-1: stimulation of IL-10 release and inhibition of nitric oxide synthesis.

Annexin-1 (ANX-1) is an anti-inflammatory protein induced by glucocorticoids. Like glucocorticoids, ANX-1 and derived peptides inhibit eicosanoid synthesis, block leukocyte migration and induce apoptosis of inflammatory cells. Cytokines may possess either pro-inflammatory, i.e. interleukin(IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-12 or anti-inflammatory properties, i.e. IL-4, IL-10. The experiments described in the present study have been performed to answer the question whether the anti-inflammatory action of ANX-1 may be mediated, at least in part, by the release of IL-10. In macrophage (J774) cell line cultures primed with lipolysaccharide (LPS), recombinant ANX-1 stimulated IL-1…