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Biomedical subjects

C Chizzolini

Publications and source records attributed to C Chizzolini.

At least 19 recordsLinked to original sources
PubMed2001

Life-threatening complications of hepatitis B virus-related polyarteritis nodosa developing despite interferon-alpha2b therapy: successful treatment with a combination of interferon, lamivudine, plasma exchanges and steroids.

Polyarteritis nodosa (PAN) is a rare vasculitis associated with hepatitis B virus (HBV) infection in a significant proportion of cases. When used to treat HBV-related PAN, immunosuppressive agents may enhance viral replication and relaspes are frequent. In recent years the use of antiviral drugs has been proposed. We report the case of a patient with HBV-related PAN who, despite 6 weeks of interferon-alpha2b (IFN-alpha2b) monotherapy, developed life-threatening complications with bowel perforation. He was thereafter successfully treated with a combination of IFN-alpha2b, lamivudine, plasma exchanges and short-term steroids. In contrast to IFN-alpha2b, lamivudine is effective in rapidly suppressing viral replication. This may be valuable in the treatment of HBV-related PAN by contributing to a faster diminution of circulating immune complex levels. This case report highlights the importance of aggressive combined therapy in patients with HBV-related PAN.

Adult↗
PubMed2001

Porphyromonas gingivalis gingipain-R enhances interleukin-8 but decreases gamma interferon-inducible protein 10 production by human gingival fibroblasts in response to T-cell contact.

Proteases produced by Porphyromonas gingivalis, an oral pathogen, are considered important virulence factors and may affect the responses of cells equipped with proteinase-activated receptors. The aim of this study was to investigate the effect of the arginine-specific cysteine protease gingipain-R produced by P. gingivalis on chemokine production by human gingival fibroblasts (HGF) and the effect of gingipain-R treatment on the subsequent contact-dependent activation of HGF by T cells. HGF incubated in the presence of purified 47-kDa gingipain-R showed increased levels of interleukin-8 (IL-8) mRNA. Cyclooxygenase-2 (COX-2) mRNA was also induced. Further exposure of HGF to activated T cells resulted in the dose- and time-dependent enhancement of IL-8 transcription and release. T-cell membrane-bound tumor necrosis factor (TNF) was the ligand inducing IL-8 production by HGF, since TNF neutralization abrogated HGF responses to T-cell contact. The enhanced IL-8 release was due, at least in part, to prostaglandin-E(2) production, which was mostly blocked by indomethacin. Gingipain-R proteolytic activity was required since heat inactivation, specific synthetic protease inhibitors, and the natural substrate competitor histatin 5 abrogated its effects. The enhanced production of IL-8 in response to T-cell contact was specific since monocyte chemotactic protein-1 (MCP-1) production was unaffected while interferon-gamma-inducible protein-10 (IP-10) was inhibited. The sum of these activities may result in the recruitment of differential cell types to sites of inflammation since IL-8 preferentially recruits neutrophils and IP-10 attracts activated T cells and may be relevant to the pathogenesis of periodontitis.

Adhesins, Bacterial↗
PubMed2000

Th2 cell membrane factors in association with IL-4 enhance matrix metalloproteinase-1 (MMP-1) while decreasing MMP-9 production by granulocyte-macrophage colony-stimulating factor-differentiated human monocytes.

Monocytes/macrophages are directly involved in tissue remodeling and tissue destruction through the release of matrix metalloproteinases (MMP). In the present study, we examined the effect mediated by contact of polarized Th cells with mononuclear phagocytes on the production of MMP-1, MMP-9, and their inhibitor. Plasma cell membranes from Ag-activated Th1 and Th2 cells were potent inducers of MMP-1 production by THP-1 cells. Cell membrane-associated TNF was found to be only partially involved in MMP-1 induction by both Th1 and Th2 cells. In Th2 cells exclusively, membrane-associated IL-4 induced MMP-1 production by THP-1 cells. This membrane-associated IL-4 effect was additive to that of TNF and was specifically observed on MMP-1 as MMP-9 production was concomitantly inhibited. Similarly, soluble IL-4 induced THP-1 cells to produce MMP-1, its effect proving additive to that of soluble TNF and to that of cell membranes of mitogen-activated HUT-78 cells. Its activity was blocked by IL-4 neutralization, and was unaffected by the presence of indomethacin. These effects on THP-1 cells were observed at protein and mRNA levels. Although inhibitory on freshly isolated peripheral blood monocytes, soluble IL-4 enhanced T cell-induced MMP-1 and inhibited MMP-9 production both at protein and mRNA levels in monocytes cultured for 7 days in the presence of GM-CSF. Thus, in contrast with previously reported effects, Th2 and IL-4 specifically induce MMP-1 production by mononuclear phagocytes at various stages of differentiation. This IL-4 activity may be relevant to pathological conditions dominated by Th2 inflammatory responses, resulting in tissue remodeling and destruction.

Adjuvants, Immunologic↗
PubMed2000

CD40-CD40 ligand (CD154) engagement is required but may not be sufficient for human T helper 1 cell induction of interleukin-2- or interleukin-15-driven, contact-dependent, interleukin-1beta production by monocytes.

To investigate whether antigen-independent, interleukin-2 (IL-2) or IL-15 activation of polarized T helper (Th) cells would result in contact-dependent activation of monocytes, living Th1 and Th2 cell clones were co-cultured with THP-1 cells or fresh peripheral blood monocytes. Under these conditions IL-1beta production was induced almost exclusively by Th1 cells and was dependent on the presence and dose of IL-2 or IL-15, and on cell-cell contact, as demonstrated by double-chamber cultures. Low levels of IL-1 receptor antagonist (IL-1Ra) were induced by Th1 and higher levels by Th2 cells. IL-10 production was similar in Th1/monocyte and Th2/monocyte co-cultures, thus arguing against preferential down-regulation of IL-1beta production by anti-inflammatory IL-10 in Th2 co-cultures. In addition, IL-4 and IL-10 neutralization did not result in enhanced IL-1beta production in Th2/monocyte co-cultures. Preferential expression on Th1 cells of CD11b correlated with their capacity to induce IL-1beta production by THP-1 cells in the presence of IL-2 or IL-15, but anti-CD11b monoclonal antibody could not inhibit this activity. Blockade of the CD40-CD40 ligand interaction resulted in inhibition of IL-1beta-inducing capacity while IL-1Ra induction was unaffected, a result previously unknown. This differential effect indicates the selective relevance of CD40-CD40 ligand engagement in inflammatory monocyte responses upon activation by T cells. CD40 ligand expression levels did not differ in Th1 and Th2 cell clones, thus indicating that additional, unidentified molecule(s) preferentially expressed by Th1 cells are involved in their IL-1beta induction capacity.

Antigens, CD↗
PubMed2000

Hypocomplementemic panniculitis with paraprotein.

Two episodes of severe panniculitis accompanied by fever and an acute phase response were the main clinical features in a patient who had an unusual IgG kappa paraprotein. Both episodes responded promptly to steroids. Complement proteins of the early classical pathway were depleted in the patient's serum, and in vitro experiments indicated that the IgG kappa paraprotein activated complement directly. The association of recurrent panniculitis and paraproteinemia-hypocomplementemia has been described in 2 other patients. It should be recognized since its response to steroids is immediate.

Acute-Phase Reaction↗
PubMed1998

Inhibition of type I collagen production by dermal fibroblasts upon contact with activated T cells: different sensitivity to inhibition between systemic sclerosis and control fibroblasts.

OBJECTIVE: To assess the role of T lymphocyte-fibroblast contact in type I collagen production by cultured dermal fibroblasts from normal individuals and from patients with diffuse systemic sclerosis (SSc). METHODS: Cell membranes were prepared from activated CD4+ and CD8+ T cells, or type 1 T helper (Th1) clones, and added to confluent fibroblast monolayers. Type I collagen production was measured in culture supernatants, and messenger RNA (mRNA) levels of type I procollagen alpha1 (pro alpha1[I]) and matrix metalloproteinase 1 (MMP-1) were evaluated by Northern hybridization analysis. RESULTS: Dose-dependent inhibition of type I collagen production was observed with CD4+ and CD8+ T cells from both SSc patients and controls. Inhibition of type I collagen was significantly less pronounced in fibroblasts from SSc patients than in fibroblasts from controls (P < 0.02). Inhibition was not reversed by the addition of exogenous transforming growth factor beta, interleukin-4, interleukin-1 receptor antagonist, anti-tumor necrosis factor, anti-CD40, or indomethacin, whereas anti-interferon-gamma (IFNgamma) reversed Th1-mediated inhibition. This inhibitory activity was specific for type I collagen, since mRNA levels of pro alpha1(I) were decreased, whereas mRNA levels of MMP-1 were strongly increased. CONCLUSION: The production of type I collagen by skin fibroblasts is specifically down-regulated by membranes from activated T cells. The contact-dependent regulatory activity exerted by T cells on fibroblasts depends, at least in part, on the presence of membrane-associated IFNgamma. However, SSc fibroblasts are more resistant to inhibition than are fibroblasts from normal individuals.

Aged↗
PubMed1998

Characterisation of the cytotoxic alloresponse of cord blood.

As compared to bone marrow, transplantation with cord blood (CB) is associated with a lower risk of GVHD. Although some cases of GVHD III have been reported, usually the grade of GVHD remains low, even when donor and recipient are not fully HLA matched. To investigate whether this is due to an intrinsic property of CB T cells, we studied the conditions under which CB CD8+ cells would be able to generate an alloresponse. In addition, we measured the cytokines secreted by the alloreactive cytotoxic T lymphocyte (CTL) clones generated. We show that: (1) the capacity of CB cells to generate alloreactive CTLs in vitro is diminished as compared to adult cells (AB); (2) in the presence of exogenous IL-2, CB cells do generate a normal alloreactive response; (3) although CB-derived CD8+ allospecific clones showed the same T1/T0 cytokine profile as the clones from AB, they secreted a lower amount of IFN-gamma; and (4) in addition, cloned CD4+ CB cells are mainly T2/T0 type, whereas AB CD4+ T cells were mainly of T1/T0 type. These data suggest that the reduced GVHD observed after transplantation with CB might be the result of the naiveness of CB T cells. After allostimulation, CB cytotoxic T cells differ from AB T cells by a higher activation threshold, a lower secretion of IFN-gamma by both CD4+ and CD8+ CB cells and their bias towards a T2 type CD4 response.

Adult↗
PubMed1997

Human Th1 cells preferentially induce interleukin (IL)-1beta while Th2 cells induce IL-1 receptor antagonist production upon cell/cell contact with monocytes.

The role of human T cells in the induction and regulation, upon cell/cell contact, of inflammatory responses by monocytic cells was investigated. The production of interleukin (IL)-1beta and IL-1 receptor antagonist (IL-1Ra) by the monocytic THP-1 cell line was measured upon contact with either Th1 or Th2 cell clones. CD4+ T cell clones specific for purified protein derivative of Mycobacterium tuberculosis, predominantly Th1 [high interferon (IFN)-gamma and low IL-4 producers], or tetanus toxoid, predominantly Th2 (low IFN-gamma and high IL-4 producers), were generated. Cell membranes from antigen-stimulated, but not from resting T cell clones induced dose-dependent cytokine production by THP-1 cells. Th1 clones induced higher levels of IL-1beta production (484-806 pg/ml) than did Th2 clones (21-114 pg/ml). In contrast, Th1 clones induced lower levels of IL-IRa (0.9-7.8 ng/ml) than did Th2 clones (7.0-49.6 ng/ml). Similar results were obtained when T cell clones were activated by cross-linked CD3 and CD28. IL-1beta production by THP-1 cells correlated with IFN-gamma production by T cell clones but was unaffected by IFN-gamma neutralization. IL-1Ra production by THP-1 cells correlated with IL-4 production by T cells and was partially inhibited by IL-4 neutralization. These data indicate that activated Th1 and Th2 cells express different molecules on the cell surface able to induce distinct pro-inflammatory (IL-1beta) or anti-inflammatory (IL-1Ra) responses in monocytes. This differential induction of molecules with opposite effects on inflammation stresses the functional heterogeneity in CD4+ T cells.

CD28 Antigens↗
PubMed1995

Antigen presentation is inhibited in vivo by betamethasone.

Aim of the present study was to assess whether betamethasone, a synthetic glucocorticoid used as immunosuppressant, could modify in vivo the antigen presentation by antigen presenting cells (APC). Interleukin-2 (IL-2) production by a T cell hybridoma specific for the hen egg white lysozyme (HEL) cultured in the presence of HEL and APC from treated or control mice was utilized as read out. Betamethasone induced a dose-dependent inhibition of antigen presentation. Fifty percent maximal response was observed with 1152 (95% confidence interval: 948-1419) resident peritoneal macrophages from untreated animals, and 5843 (4700-7445, 21, 235 (12,857-43,705), 28,313 (20,847-40,955) macrophages from mice injected for 3 days with betamethasone 10, 25, and 50 mg/kg respectively. Similar findings were obtained with spleen cells. When given for 3 days at 25 mg/kg, betamethasone reduced the number of cells recovered from the peritoneum by approximately half and from the spleen by one order of magnitude. One day vs. 3 days treatment resulted in similar recovery of cells but lower inhibition of APC function. In the experimental conditions utilized, no carryover of betamethasone with APC could be demonstrated and no reversal of inhibition was observed by increasing the antigen concentration. The data here presented demonstrate that short curses of high dose betamethasone specifically impair antigen presentation. Thus, this mechanism appears to be involved in the immunosuppressant activity of betamethasone.

Animals↗
PubMed1995

Inhibition by cholesterylphosphorylserine of T-cell-mediated immune responses in mice.

The synthetic analogue of phosphatidylserine, cholesterylphosphorylserine (CPHS) inhibits T-cell-mediated immune responses in mice. Tested in cultured mouse spleen cells, CPHS inhibits concanavalin A-induced activation of DNA synthesis (IC50, 3.5 microM). Injected i.p. during the efferent phase, CPHS (25-100 mg/kg) inhibits the manifestations of delayed-type of hypersensitivity. The compound (25 mg/kg i.p., daily) reduces the acute graft-versus-host reaction when given for 5 days to donor mice before the isolation of spleen cells used for the inoculum. These data suggest that the addition of a phosphorylserine group to a steroid ring may produce immunoregulatory compounds.

Adjuvants, Immunologic↗
PubMed1994

Cerebrovascular and neurological disorders associated with antiphospholipid antibodies in CSF and serum.

Paired serum and cerebrospinal fluid (CSF) samples from 70 patients with inflammatory and non-inflammatory neurological diseases, as well as 10 sera from patients with primary antiphospholipid syndrome (PAS), six of which presented with cerebrovascular ischemic syndromes, were studied for the presence of anticardiolipin antibodies (ACA) of the G and M classes. PAS sera and some selected paired CSF and serum specimens, were also analyzed for the presence of anti-phosphatidylserine (PS) and anti-phosphatidylethanolamine (PE) antibodies. High levels of IgG and IgM ACA were synthesized intrathecally only in patients with neurosyphilis. Patients with other infectious or inflammatory neurological diseases very rarely showed detectable levels of ACA in serum and/or CSF. ACA were found not only in patients with untreated PAS but also in the serum of 3/7 patients with migraine, thus confirming a relationship between ACA and vascular disorders. The search for PS and PE antibodies disclosed that in PAS patients the serum titers of these antibodies mirrored ACA IgG and IgM titers, while they were never found in the CSF.

Adolescent↗
PubMed1994

Lipid mediators of immune reactions: effect of a linked phosphorylserine group.

Immunoregulation by lipids containing the phosphorylserine (PHS) group has been studied in rodent peritoneal mast cells and human peripheral blood lymphocytes. When PHS is linked to a phospholipid backbone (mono- and diacylglycerol), mast cell activation is produced. However, the effect decreases linking the PHS group to long chain alkanols and is abolished in cholesteryl-PHS, showing that the acylglycerol moiety participates in mast cell activation. Phospholipids containing the PHS group inhibit proliferation of activated peripheral blood lymphocytes. In contrast to mast cells, this effect is retained in alkyl-PHS and is enhanced in cholesteryl-PHS, indicating that in this case the PHS group is the main effector. Among non-phospholipid PHSs, cholesteryl-PHS has been the most interesting since it associates lack of mast cell activation and high inhibitory activity on peripheral blood lymphocytes. This selectivity suggests that this compound may have a potential as an immunosuppressive agent.

Animals↗