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F De Benedetti

Publications and source records attributed to F De Benedetti.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cytokines in juvenile rheumatoid arthritis.

Most data concerning the role of cytokines in chronic arthritides have been obtained in adult rheumatoid arthritis. In this paper we review the available evidence regarding the role of the inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor in juvenile rheumatoid arthritis, focusing in particular on the differences among the various onset types. Results from the analysis of cytokine expression may provide the basis for the use of specific anticytokine treatment. Recent clinical trials in adult rheumatoid arthritis have demonstrated the feasibility and clinical usefulness of these treatments.

Arthritis, Juvenile↗
PubMed1997

Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis.

OBJECTIVE: To evaluate quantitative or qualitative differences in synovial fluid (SF) cytokine levels among patients with systemic juvenile rheumatoid arthritis (JRA), antinuclear antibody positive pauciarticular JRA, or adult RA. METHODS: SF levels of interleukin 1alpha (IL-1alpha), IL-1beta, IL-1 receptor antagonist (IL-1Ra) IL-11, tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 (sTNFR1), leukemia inhibitory factor (LIF), all measured by immunoassays, and of IL-6, measured with a bioassay using B9 cells, were evaluated in 11 patients with systemic JRA, 24 with pauciarticular JRA, and 22 adult patients with RA. RESULTS: SF IL-6 levels were significantly higher in patients with systemic JRA than patients with pauciarticular JRA (p = 0.003) or RA (p = 0.002). IL-1alpha was detectable in 12/24 SF samples from pauciarticular JRA, in 2/22 SF from RA, and in no sample from systemic JRA (p = 0.004 vs RA; p = 0.005 vs systemic JRA). SF IL-11 levels were significantly higher in patients with RA than patients with systemic JRA (p = 0.012) or pauciarticular JRA (p = 0.005). We found no significant differences in SF levels of IL-1beta, IL-1Ra, TNF-alpha, sTNFR1, or LIF. CONCLUSION: In systemic JRA, SF levels of IL-6 are significantly higher than in pauciarticular JRA or in RA; IL-1alpha is present in a significant proportion of patients with pauciarticular JRA, but not in those with RA or systemic JRA.

Adolescent↗
PubMed1995

Identification of HLA-unrestricted CD8+/CD28- cytotoxic T-cell clones specific for leukemic blasts in children with acute leukemia.

We report on the identification of 57 T-cell clones (TCC) cytolytic to autologous leukemic blasts (LB) but not autologous bone marrow remission cells. LB-reactive TCC were obtained from 3 children with acute leukemia at remission; all expressed the same phenotype, CD3/TCR alpha beta/CD8+, but were heterogeneous for the expression of V beta T-cell receptor (TCR) V region chains, thus showing that these cells were not derived from the expansion of a single clone. Cytolytic activity of LB-reactive TCC was not restricted to autologous LB because they were also able to lyse phenotypically similar allogeneic LB but not bone marrow remission cells of the same patients. Neither autologous nor allogeneic LB used in the present study as stimulator and target cells expressed CD80 (B7/BB-1) antigen, and LB-reactive TCC were CD28-. Cytolytic activity of the clones was only inhibited by anti-CD11a (LFA-1) mAb but not by mAbs specific for HLA class I and II, CD3, CD8, or TCR alpha beta. In conclusion, these data suggest that a subset of apparently HLA-unrestricted, CD3/TCR alpha beta/CD8+ CD28- cytotoxic T lymphocytes, which use a TCR/CD3-independent recognition pathway, is primarily involved in antitumor immune response of children with acute leukemia at remission, possibly contributing to the control of minimal residual disease.

Antibodies, Monoclonal↗
PubMed1995

Lack of temporal association of iridocyclitis with IgG reactivities to core histones and nucleosome subparticles in pauciarticular juvenile chronic arthritis.

This study aimed to measure IgG reactivities to DNA-free nucleosome subparticles (H2AH2B, H3H4) and nucleosome subparticles (H2AH2B-DNA, H3H4-DNA) and to evaluate the temporal relation of these reactivities, as well as those to single core histones, with iridocyclitis (IC) in patients with antinuclear antibody positive (ANA+) pauciarticular juvenile chronic arthritis (JCA). Reactivities to nuclear substrates were determined by enzymatic immunoassays in 120 sera from 45 children with ANA+ pauciarticular JCA. Significantly elevated IgG levels to H3 and H4, to DNA-free nucleosome subparticles, and to the nucleosome subparticle H3H4-DNA were present in patients with ANA+ pauciarticular JCA; no evidence of recognition of conformational epitopes was found. In both horizontal and follow-up studies, no relation between the reactivities studied and the development, presence, or history of IC was found. Our results show the absence of a relation of antibodies to histone molecules or to nucleosome subparticles with IC in patients with ANA+ pauciarticular JCA.

Adolescent↗
PubMed1995

Circulating levels of interleukin-6, interleukin-8, and tumor necrosis factor-alpha in children with autoimmune hepatitis.

Circulating levels of the proinflammatory cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured in 13 children with autoimmune hepatitis (AIH) (seven with type 1 and six with type 2). In untreated children with type 1 AIH, TNF-alpha, IL-6, and IL-8 levels were elevated when compared to those of healthy controls (p < 0.005, p < 0.02, p = 0.06, respectively), whereas in children with type 2 AIH, cytokine levels were normal in all except one sample. A significant decrease in circulating IL-6, IL-8, and TNF-alpha was observed when patients were evaluated during a subsequent remission. We found no significant correlation of cytokine levels with alanine aminotransferase (ALT) activity, total serum gamma-globulins, or prothrombin activity. In patients with cirrhosis, serum IL-8 and IL-6 levels were higher (significantly in the case of IL-8) than those of patients without cirrhosis. In conclusion, activation of the in vivo production of the proinflammatory cytokines IL-6, IL-8, and TNF-alpha appears to be associated with type 1 but not with type 2 AIH.

Adolescent↗
PubMed1995

Elevated circulating interleukin-7 levels in patients with systemic juvenile rheumatoid arthritis.

OBJECTIVE: Since interleukin-7 (IL-7) has been shown to induce monocyte production of IL-1, IL-6, IL-8, and tumor necrosis factor-alpha, we investigated plasma and synovial fluid levels of IL-7 in patients with juvenile rheumatoid arthritis (JRA). METHODS: IL-7 levels were measured using an ELISA in 60 patients with JRA and in 25 patients with other rheumatic disorders (ORD). RESULTS: In patients with systemic JRA, but not in patients with polyarticular or pauciarticular JRA or with ORD, plasma IL-7 levels were significantly higher (p < 0.0001) than those of healthy controls. IL-7 was undetected in all synovial fluid tested. Among patients with systemic JRA, those with persistent systemic symptoms had IL-7 levels significantly higher (p < 0.01) than those of patients in which systemic symptoms subsided. CONCLUSION: Plasma IL-7 levels are elevated in patients with systemic JRA and are associated with the presence and severity of systemic symptoms.

Adolescent↗
PubMed1994

Reversal of nephrotic syndrome due to reactive amyloidosis (AA-type) after excision of localized Castleman's disease.

The patient (TAL), a chronic asymptomatic HBV carrier with HBsAg-anti-HBsAg circulating immune complexes, was admitted to our hospital because of a nephrotic syndrome due to renal amyloidosis. There was no family history of hereditary amyloidosis. Recurrent arthralgias, asthenia, and weight loss were the prominent clinical features. Laboratory test results showing that severe chronic inflammatory activity had been present for 6 years. Interleukin-6 (IL-6) serum concentration was 10 times normal and C-reactive protein was 1.9 mg/ml. A complex immunological picture was also present (immune complex formation, exuberant B-cell reactivity, and decrease in the number of CD4 T cells). A localized form of Castleman's disease (CD) (plasma-cell type) was diagnosed by surgical excision of a giant axillary lymph node. AA amyloid was present in the blood vessels. Within 60 days after excision of the mass, the systemic symptoms subsided, laboratory signs of inflammatory activity disappeared and IL-6 serum concentration returned to normal, thus establishing a causal relationship between the localized Castleman's disease, elevated IL-6 concentration and the chronic inflammation responsible for AA amyloidosis. At 10 months of follow-up, the nephrotic syndrome has reversed, kidney function has slowly ameliorated, and the patient has gained 12 kg. Abdominal fat aspirates drawn to search for amyloid, positive before surgery, were subsequently negative. The latter finding, and the remission of the nephrotic syndrome, provided strong evidence for regression of the amyloid deposits. However, the HBsAg-anti-HBsAg immune complexes and depression of T-helper cell activity persist. This immunological derangement is therefore not a consequence of CD. Chronic stimulation of the immune system due to the patient's inability to eliminate HBV, in the contest of perturbed immunity, may have favored the genesis of the lymphadenopathy.

Adult↗
PubMed1994

Hypocomplementemic urticarial vasculitis syndrome with severe systemic manifestations.

We describe two children with clinical and laboratory features of hypocomplementemic urticarial vasculitis syndrome. Both patients had severe, life-threatening manifestations: rapidly progressive glomerulonephritis (patient 1) and pulmonary hemorrhage (patient 2). We conclude that this syndrome may be a potentially severe multisystem disease.

Adolescent↗
PubMed1994

Immune responses to the Escherichia coli dnaJ heat shock protein in juvenile rheumatoid arthritis and their correlation with disease activity.

Patients with juvenile rheumatoid arthritis frequently have abnormal immune responses to the hsp65 class of bacterial heat shock proteins. However, lymphocytes from children with other inflammatory diseases may also recognize hsp65, and the role of these antigens in juvenile rheumatoid arthritis remains controversial. We have studied humoral and cellular immune responses to a distinct, recently described bacterial heat shock protein, designated dnaJ. The Escherichia coli dnaJ gene was cloned and expressed, and the purified recombinant protein was used as an antigen. Neither normal children nor children with various chronic inflammatory diseases had lymphocyte proliferative responses to recombinant dnaJ. However, lymphocytes from patients with polyarticular, pauciarticular, and systemic manifestations of juvenile rheumatoid arthritis responded strongly to the antigen. Cellular immune responses to dnaJ were higher in synovial fluid than in blood and higher in children with active disease than in children in remission. These data show that increased immune reactivity to dnaJ is characteristic of juvenile rheumatoid arthritis and that the magnitude of the immune response is linked to disease activity. The results suggest that an abnormal immune response to antigens on commensal gut bacteria may contribute to the generation of chronic inflammation in juvenile rheumatoid arthritis.

Adolescent↗
PubMed1994

Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis.

By using a sandwich ELISA, soluble human IL-6 receptor (sIL-6 R) levels were measured in the sera of 20 healthy children and of 25 patients with systemic juvenile rheumatoid arthritis (JRA). In patients with systemic JRA, serum sIL-6 R levels (114.6 +/- 37.7 ng/ml) were significantly lower (P < 0.01) than those of healthy children (161.2 +/- 45.5 ng/ml). Serum sIL-6 R levels were negatively correlated (r = -0.610, P < 0.001) with serum IL-6 levels measured with the B9 cells. The serum IL-6/sIL-6 R complex was detected using an ELISA based on a monoclonal antibody to IL-6 for capture and on a monoclonal antibody to human sIL-6 R for detection. Healthy controls had little, if any, detectable serum IL-6/sIL-6 R complex (OD 0.024 +/- 0.027), while the majority of patients with systemic JRA presented measurable serum IL-6/sIL-6 R complex (OD 0.492 +/- 0.546). IL-6 levels estimated in the circulating IL-6/sIL-6 R complexes were in the range of nanograms per milliliter and approximately 20-fold higher than those measured by the B9 cells. Since serum C-reactive protein concentrations were much more correlated with serum levels of IL-6/sIL-6 R complexes (r = 0.713, r2 = 0.51, P < 0.0001) than with the serum IL-6 levels measured with the B9 cells (r = 0.435, r2 = 0.19, P = 0.05), the large quantities of serum IL-6 present in IL-6/sIL-6 R complexes appear to be biologically relevant in vivo, at least as far as the induction by IL-6 of acute phase protein production.

Adolescent↗
PubMed1994

Immunoactivation by pidotimod in children with recurrent respiratory infections.

The therapeutic activity and safety of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6), a new synthetic "biological response modifier", were examined in a double-blind, placebo-controlled, multicentre trial in 101 children, including 53 boys and 48 girls aged 2-13 years (mean +/- SD: 4.7 +/- 2.1 years) with a history of recurrent respiratory infections (RRI). Pidotimod (400 mg/day) or placebo were administered orally for 60 consecutive days, followed by a further 60-day follow-up period. The trial was completed by 89.1% of patients. The results indicate that pidotimod has a beneficial effect in children with recurrent respiratory infections: the percentage of patients presenting symptoms affecting the upper and lower airways was significantly lower after treatment with the active drug than after treatment with placebo. Relevant side effects were not reported during the trial. An evaluation of the expression of CD25 (after in vitro stimulation of circulating mononuclear cells with PHA) before and after treatment with the two products revealed a significant increase in CD25+ cells in the group treated with pidotimod but not in the group treated with placebo.

Adjuvants, Immunologic↗
PubMed1993

CD5-positive B cells in type 1 (insulin-dependent) diabetic children.

We have measured CD5+ B cell levels in the peripheral blood of 35 type 1 (insulin-dependent) diabetic children, aged 1.1-21.2 years (10.7 +/- 4.6 years). Patients were divided into two groups according to disease duration (group I < 6 months and group II > 1.5 years). Group I included 18 patients and group II 17 patients. Thirty-nine healthy subjects, comparable for age and sex, served as controls. CD5+ B cells were identified by double immunofluorescence staining with rhodamine-conjugated rabbit anti-human immunoglobulin and with a mouse anti-CD5 monoclonal antibody revealed by a fluorescein-conjugated goat anti-mouse immunoglobulin. We found that CD5+ B cell levels (expressed as percentages of peripheral blood B lymphocytes) were significantly higher in group I (median 24; range 4-48) than in controls (median 14; range 0-36, P < 0.001) and in group II (median 4; range 0-20, P < 0.001). A follow-up study of 12 group I patients showed a significant decline in CD5+ B cell levels. The data obtained in our diabetic patients suggest that CD5+ B cells are expanded in the early phase of type 1 diabetes mellitus and may play a role in the autoimmune process of the disease.

Adolescent↗
PubMed1993

Correlation of serum neopterin concentrations with disease activity in juvenile dermatomyositis.

Serum neopterin concentrations were measured in 15 patients with juvenile dermatomyositis and their correlation with the severity of muscle impairment was evaluated. Neopterin concentrations were measured by radioimmunoassay. When compared with controls (median 0.75 ng/ml; range 0.33-1.18), serum neopterin concentrations were increased in patients with active juvenile dermatomyositis (median 3.21 ng/ml; range 0.95-13.81), but not in patients during remission (median 0.81 ng/ml; range 0.55-1.34). In horizontal and longitudinal studies, serum neopterin was significantly correlated with the severity of muscle strength impairment, whereas serum muscle enzyme values were not. These data suggest that measurement of serum neopterin may be used, together with clinical examination, to guide the treatment of patients with juvenile dermatomyositis.

Adolescent↗
PubMed1993

Tumor necrosis factor in plasma and peritoneal fluid of women with and without endometriosis.

To determine whether in vivo levels of tumor necrosis factor a in plasma and peritoneal fluid differ in infertile subjects with and without endometriosis, peripheral blood and peritoneal fluid samples were collected in 94 women undergoing laparoscopy for infertility. Quantitative determinations of tumor necrosis factor a were performed by an enzyme immunoassay test. Tumor necrosis factor a levels were below the detection limit (10 pg/ml) in plasma and peritoneal fluid of 42 (91%) and 30 (90%) patients with endometriosis and 40 (83%) and 31 (91%) subjects without the disease, respectively. In our series, plasma and tumor necrosis factor a levels were not different in infertile women with and without endometriosis.

Adult↗
PubMed1991

Induction of transforming growth factor-beta 1 (TGF-beta 1), receptor expression and TGF-beta 1 protein production in retinoic acid-treated HL-60 cells: possible TGF-beta 1-mediated autocrine inhibition.

Treatment of HL-60 cells, a human promyelocytic leukemia cell line, with the vitamin A derivative retinoic acid (RA) for 7 days resulted in a dose-dependent decrease in proliferation and increase in granulocytic differentiation. The role of transforming growth factor-beta 1 (TGF-beta 1), a protein with pleiotropic effects on the proliferation and differentiation of various cell types, was examined during RA-induced differentiation of HL-60 cells. Although TGF-beta 1 alone had little effect on proliferation or differentiation of HL-60 cells, addition of TGF-beta 1 to HL-60 cells treated with a suboptimum concentration of RA (1.0 nmol/L) resulted in a marked decrease in proliferation with no effect on granulocytic differentiation. Studies of the mechanism of RA-induced TGF-beta sensitivity showed that although untreated HL-60 cells expressed low levels of TGF-beta 1 binding proteins on the cell surface, the levels were increased in a dose-dependent manner after RA treatment. Maximum induction was achieved after treatment with 10 nmol/L RA and consisted predominantly of the 65-Kd TGF-beta 1 receptor type. Moreover, RA treatment also resulted in a dose-dependent increase in both TGF-beta 1 steady-state mRNA expression and production of active TGF-beta with maximum induction at 10 nmol/LRA. RA treatment of HL-60 cells had no effect on TGF-beta 2 and TGF-beta 3 mRNA expression. These data suggest that the effects of RA may be mediated by a TGF-beta 1-mediated autocrine antiproliferative loop during differentiation of HL-60 cells.

Cell Differentiation↗