Serum sTNFR1 Research Articles

Relation between depression and circulating immune products in patients with advanced colorectal cancer.

We have previously suggested that colorectal liver metastases might produce 'toxins' that reduce both quality of life (QoL) and survival. In this study we assessed whether QoL in patients with such metastases was related to immune activation, as determined by increased serum levels of interleukin 6 (IL6), soluble tumour necrosis factor receptor 1 (sTNFr1), soluble interleukin 2 receptor alpha (sIL2r alpha) or the interferon-gamma marker neopterin. Serum IL6, sTNFr1, sIL2r alpha, neopterin, alkaline phosphatase and carcinoembryonic antigen levels, liver metastasis volume, and QoL (Hospital Anxiety and Depression [HAD] scale, Rotterdam Symptom Checklist [RSC], and Sickness Impact Profile [SIP]) were measured in 43 patients. There were significant positive correlations between serum sIL2r alpha and HAD depression score (r = 0.66, P = 0.0001), RSC physical symptom score (r = 0.46, P < 0.01), and SIP score (r = 0.47, P = 0.009). Multiple regression analysis suggested that serum sIL2r alpha level was a significant independent predictor of HAD depression score. Although survival was shorter (logrank test P < 0.05) where sIL2r alpha, sTNFr1 and IL6 levels were higher, the ability of sIL2r alpha to predict HAD depression score was independent of survival.

EVIDENCE FOR INTERLEUKIN-1 RECEPTOR ANTAGONIST (IL-1RA) IN PERITONEAL FLUIDS AS AN EARLY MARKER FOR ACUTE REJECTION AFTER PEDIATRIC LIVER TRANSPLANTATION

153 Background: Interleukin-1 takes part in the immune response mediating acute cellular rejection after liver transplantation. The naturally occuring inhibitor of IL-1 activity has been found to be a secreted molecule known as IL-1 receptor antagonist (IL-1ra) capable of blocking the IL-1 receptor without resulting in signal transduction. The aim of this study was to investigate the value of IL1-ra secretion in serum and peritoneal fluids in comparison with common markers for acute graft rejection. Patients and methods: 13 children (median age = 11mo) were followed in the first two weeks after orthotopic liver transplantation. Serum and drainage fluids samples were daily obtained for IL-1ra, IL-2r, IL-15, sTNFr2 and IL-6 quantification (immunoassay). In case of acute cellular rejection (biopsy proven) IL-1ra levels were correlated to elevation of liver enzymes, αGST and different cytokines. Results: 3 children were found to have acute cellular rejection and had significant elevation of serum liver enzymes, αGST, IL-2r, IL-15, sTNFr2 and IL-1ra up to 24 hours before biopsy. No significant increase in IL-6 levels were observed. Compared to these parameters levels of IL-1ra in drainage fluids increased 48 hours before biopsy proven rejection:TableConclusions: Quantification of IL-1ra in peritoneal fluids seems to indicate rejection after liver transplantation 24 hours earlier compared to serum. These findings need to be confirmed by a greater cohort of patients.

The role of tumor necrosis factor receptors in cell signaling and the significance of soluble form levels in the serum.

Two types of tumor necrosis factor membrane receptors (TNF-R) have been identified, namely 55 and 75 kDa TNF-R. Soluble forms of these receptors are present in the human serum. Recent findings on the role of these two TNF-R in biological cell signaling and the clinical significance of the serum levels of soluble TNF-R (sTNF-R) were reviewed. It is not the uptake of TNF molecules into cells but rather the molecular capping of TNF-R on the cell membrane that initiates the biological activity of TNF. The 55 kDa TNF-R mediates major bioactivities of TNF, while the significance of 75 kDa TNF-R remains unclear. We herein suggest a new concept of the role of these two TNF-R: The 75 kDa TNF-R signal appeared to enhance that of 55 kDa TNF-R in the induction of ICAM-1 expression on HL-60 human promyelocytic leukemic cells. High serum levels of sTNF-R are reported in patients with malignancy, endotoxin shock, pneumonia, and autoimmune diseases. However, the source of elevated serum sTNF-R remains unclear. Studies on the clinical usefulness of serum sTNF-R levels as cancer and inflammation markers are now being carried out.

Correlation between serum levels of soluble tumor necrosis factor receptor and disease activity in systemic lupus erythematosus.

To determine the value of measurement of serum soluble tumor necrosis factor receptor (sTNFR), compared with established parameters such as anti-double-stranded DNA, in monitoring systemic lupus erythematosus (SLE) disease activity, and to determine whether serum sTNFR are bioactive and can effectively inhibit TNF bioactivity. Fifty-three consecutive ambulatory or hospitalized SLE patients and 140 consecutive healthy subjects were enrolled in a prospective cohort study. Serum levels of sTNFR were measured by a unique 2-sided capture enzyme-linked immunosorbent assay using mouse monoclonal antibodies and rabbit antisera against the sTNFR. The mean +/- SD concentrations of both the p55 (type I) and p75 (type II) soluble receptors were significantly higher in a group of 46 SLE patients than in controls: 1.89 +/- 0.89 ng/ml versus 0.77 +/- 0.19 ng/ml and 7.25 +/- 3.89 ng/ml versus 3.02 +/- 0.57 ng/ml, respectively (P < 0.0001 for both). The incidence and the extent of the increase among the healthy subjects and these patients (as well as in 7 additional patients on whom sequential studies were performed) correlated with disease activity more than did the occurrence of serum anti-DNA antibodies (correlation coefficients with disease activity 0.81 and 0.85 for p55 and p75 sTNFR, respectively, and 0.51 for anti-DNA antibodies). The increase in sTNFR levels seems to reflect, largely, enhanced formation, and only to a minor extent, reduced clearance due to impairment of renal function. Sera of the SLE patients had a marked inhibitory effect on the in vitro cytocidal activity of TNF, and this was shown to result entirely from their higher sTNFR receptor concentration. An increase in serum levels of sTNFR may become a useful marker for SLE activity since it shows a stronger correlation than do any other laboratory or clinical parameters employed presently in the daily clinical setting. At the concentrations attained in the serum of SLE patients, sTNFR effectively inhibit the bioactivity of TNF and may thus be a significant determinant of the intensity of the manifestations of SLE.