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Background Platelet functional abnormalities are commonly found in patients with chronic liver disease; however, their nature and clinical significance are still a matter of discussion. Methods Soluble P-selectin (sP-selectin, a marker of in vivo platelet activation) levels, lipid pattern, and clotting activity were investigated in 39 patients with histologically confirmed chronic C hepatitis. Results Serum factor VIIc ( P3/μL). Platelet-associated immunoglobulin G (PAIgG) was present in 30.8% of patients. Plasma sP-selectin levels were higher in hepatitis C patients compared with controls ( PConclusions The results obtained in this study support the hypothesis that HCV infection might be directly responsible for a condition of in vivo platelet activation in patients with chronic C hepatitis.

The acute-phase response is the answer of the organism to a disturbance of its homeostasis and is characterized by dramatic changes in the concentration of some plasma proteins defined as acute-phase proteins. In recent years several data have shown that interleukin-6 (IL-6) is the major inducer of acute-phase protein synthesis in human hepatocytes. Recently, we demonstrated higher IL-6 serum levels in head and neck cancer (HNC) patients than in healthy subjects. In the present study we examined the relationship between levels of IL-6 and of several acute-phase proteins, including C-reactive protein (CRP), alpha 1-antitrypsin (ATT), alpha 1-acid glycoprotein (AAG), haptoglobin (HPT) and fibrinogen. Eighteen patients were studied and had squamous cell carcinoma of the larynx (n = 9), oral cavity (n = 4), oropharynx (n = 3) and hypopharynx (n = 2). Proteins were measured at three time points before and three time points after surgery. Significant (P0.0001) relationships were found between IL-6 and CRP (r = 0.69), and fibrinogen (r = 0.51), whereas no correlation was found with AAT (r = 0.13, P = 0.56), AAG (r = 0.38; P = 0.07) and HPT (r = 0.16; P = 0.46). These data strongly suggest that IL-6 may play a key role in acute-phase protein synthesis in HNC and in regulation of the complex host response to malignancies.

Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are frequently detected in sera from patients affected by systemic lupus erythematosus (SLE). However, the role of antiphospholipid antibodies (aPL) in thrombus formation has not been defined as yet.Twenty-two patients affected by SLE, all fulfilling the 1982 ARA revised criteria, and twenty healthy subjects were investigated for the presence of LA, aCL and other aPLs. Monocyte procoagulant activity-PCA (Tissue Factor production) was evaluated by one stage plasma recalcification time. In all patients the plasma levels of F1 + 2 and of plasmin ogen activator inhibitor (PAI) were also determined. Monocyte PCA was significantly higher in SLE patients with LA and/or aCL in comparison to SLE patients without LA and/or aCL ( p < 0.01) and to controls ( p < 0.05). However, no connection was observed between PCA expression by mononuclear cells and LA or aCL levels. No differences in F1 + 2 and PAI plasma levels were found between SLE patients with or without aPL and controls. In our SLE patients LA and/or aCL positivity appears strictly related to an increased monocyte activation that could play an important role in the occurrence of thrombotic events.

To the Editor. —In a recent article published in the January issue of theArchives, Clayman et al 1 described the possible correlation among serum levels of acute-phase proteins and in vitro serum modulation of the lymphokine-activated killer cell induction phase and in vivo interleukin 2 (IL-2)-induced toxicity in patients with head and neck cancer who are receiving IL-2/interferon alfa immunotherapy. The authors, in agreement with others, 2 found elevated levels of such proteins in head and neck cancer patients before therapy was started and suggested the central role of IL-1 in the control of their production and its modulation by the recombinant cytokines used for therapy. In this article, however, the possible role of IL-6 in controlling liver production of acute-phase protein levels in the serum has not been taken into account. Interleukin 6 is a multifunctional cytokine with pleiotropic action that regulates the acute-phase response of the organism

In patients with advanced head and neck squamous cell carcinoma (HNSC), evidence of cell-mediated immunity and monocyte functional abnormalities has been reported. We studied the production of interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) by peripheral blood monocytes from 22 patients with HNSC (12 larynx and ten oral cavity cancers) in comparison with monocyte cytokine production of age-matched healthy subjects. Pure monocytes were incubated with and without lipopolysaccharides (LPS) (10 micrograms ml-1) for 4 h at 37 degrees C and IL-1 beta and IL-6 concentrations were determined in supernatants by specific ELISA. There was no significant difference in IL-1 beta levels in monocyte supernatants from cancer in comparison to control subjects; conversely, a higher IL-6 production by unstimulated and LPS-activated cells from HNSC patients than from controls was found. No relationship was observed between cytokine production and cancer stage. The regression analysis evidenced a significant correlation between IL-1 beta and IL-6 monocyte-release in HNSC patients and in controls, so suggesting a possible autocrine control of IL-6 production by other cytokines.

Plasma soluble P-selectin (sP-selectin), β-thromboglobulin (β-TG), von Willebrand Factor (vWF), prothrombin factor 1+2 (F1+2), IL-6 and IL-1β levels were analyzed in 35 consecutive patients with polygenic type IIa hypercholesterolemia (HC) and 35 age- and sex-matched healthy subjects. sP-selectin (p < 0.005), β-TG (p < 0.05) and IL-1β (p < 0.02) levels were higher in HC patients than healthy subjects whereas no significant difference was observed for vWF. sP-selectin directly correlated with β-TG (p < 0.05) and IL-1β levels (p < 0.005), but not with the other variables analyzed. A direct correlation was observed between F1+2 and IL-6 (p < 0.05), total cholesterol (p < 0.05) or LDL cholesterol (p < 0.05). We conclude that HC is associated with an increase of plasma sP-selectin levels, and that sP-selectin may be considered as a marker of in vivo platelet activation in type IIa polygenic HC. The correlations observed among the variables analyzed in the study suggest that proinflammatory cytokines might play a role in the prothrombotic state often associated with HC.

Stimulated monocytes are involved in blood clotting and fibrin dissolution by synthesizing tissue factor (TF) and fibrinolytic components such as plasminogen activator inhibitor type 2 (PAI-2). Heparin interacts with smooth muscle cells, platelets, and endothelial cells and specifically binds to human monocytes. In endothelial and smooth muscle cells, heparin selectively inhibits collagenase and tissue plasminogen activator gene expression. To investigate (1) heparin's influence on the hemostatic system by its interactions with plasma factors and cellular elements and (2) to determine its effects on gene expression in blood circulating cells, we studied the effect of heparin on TF and PAI-2 protein and mRNA in human lipopolysaccharide (LPS)- or interferon-gamma (IFN-gamma)-stimulated monocytes. TF and PAI-2 proteins were investigated by ELISA and by assaying procoagulant activity. The mRNA study was carried out by an initial PCR screening followed by a Northern blot semiquantitative analysis. Heparin (0.5 U/mL) inhibited both TF and PAI-2 production and gene expression. The contemporaneous protein and mRNA decrease (TF and PAI-2 protein 22 and 42%, respectively; suggests that this action is, at least partially, at the transcriptional level. The effect is not specific for heparin and is not demonstrated by other glycosaminoglycans (chondroitin-4-sulfate or dermatan sulfate). This action may be relevant for the antithrombotic activity of heparin in cell-mediated blood clotting activation.

Objectives: The purpose of this study was to investigate the relationship between hypercholesterolemia and superoxide anion production. Background: Experimental studies demonstrated that hypercholeste-rolemia is associated with enhanced cellular superoxide anion (O2- ) production. Aim of the study was to assess whether the same pheno-menon occurs in humans. Methods: Lipid profile and platelet O2- production were measured in 28 patients with hypercholesterolemia, compared with 25 age- and sex-matched healthy subjects, and in 21 out of the 28 patients after 8-week treatment with 10 mg/day atorvastatin (a HMGCoA reductase inhibi-tor). In order to assess the mechanism by which LDL cholesterol inter-feres with platelet production of O2- , human platelets were incubated with LDL cholesterol in the presence of either an inhibitor of the phos-pholipaseA2 enzyme, AACOCF3, or an inhibitor of NADH/NADPH oxidases, DPI. Results: O2- platelet generation was significantly higher (p

Background The finding that expression of metalloproteinases (MMPs) is induced in atherosclerotic plaques prone to rupture suggests the possibility that patients with atherosclerotic diseases would show enhanced blood levels of MMPs and that MMPs might represent a potential inflammatory risk factor for atherosclerosis. Therefore, the present study was aimed at verifying whether MMPs may represent sensitive markers of inflammation in patients with coronary artery disease. Methods MMP-2, MMP-9, interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen levels were measured in blood samples obtained from 66 cases with previous acute myocardial infarction and 66 control subjects similar for age, sex, and major atherosclerotic risk factors but without history or evidence of atherothrom-botic diseases. Results Biohumoral markers of inflammation and MMP-9 levels were significantly elevated in cases compared with controls (median values 40.6 versus 9.8 ng/mL; p < .0001), whereas MMP-2 levels did not differ between the two groups (median values 839 versus 873 ng/mL; p = .53). A direct correlation was found among MMP-9, CRP, IL-6, and fibrinogen levels. Conditional logistic regression analysis showed that MMP-9 is related to myocardial infarction (p = .006) even after adjusting for cardiovascular medications and CRP. Conclusion These findings suggest that measurement of serum MMP-9 levels may represent a novel marker of inflammation in patients with known coronary artery disease and might provide an index of plaque activity in this clinical setting.