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PubMed1993

Solubility characteristics of the ideal agent for measurement of cardiac output by soluble gas uptake methods.

Measurements of the rate of uptake of soluble gases such as nitrous oxide or acetylene has been used as the basis of a method of cardiac output estimation since 1912. Using theoretical models of single, multiple and rebreathing techniques of cardiac output measurement, we determined the effect of solubility in blood and lung tissue on the changes in the final expired concentration of the gas. Decreasing lung tissue solubility increased the sensitivity of all three models to cardiac output changes. When the lung tissue/blood partition coefficient was 1, the optimum blood/gas partition coefficients were 2.6 for the single-breath model, 4.1 for the three breath-model and 3.5 for the rebreathing model. A selection of gases, including volatile anaesthetic agents was studied using the same models. Under most conditions, enflurane approximated most closely to the requirements for an ideal agent for use in this technique of cardiac output measurement.

Anesthetics↗

PubMed2005

Serum and follicular fluid levels of soluble Fas, soluble Fas ligand and apoptosis of luteinized granulosa cells in PCOS patients undergoing IVF.

BACKGROUND: There are limited data about the levels of soluble apoptotic factors and their modulation with therapeutic regimens in IVF cycles. The aim of the current study was to determine follicular fluid, and serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) in PCOS patients undergoing IVF/ICSI cycles; also to investigate the effects of metformin on these factors and on apoptosis of luteinized granulosa cells. METHODS: We investigated the serum and follicular fluid levels of sFas and sFasL in patients with PCOS (n = 28) and compared them with those of the patients with infertility due to male factor (n = 12) undergoing IVF cycles. Effects of metformin therapy on these parameters and apoptosis of luteinized granulosa cells were also investigated among the patients with PCOS. RESULTS: Serum levels of sFas were significantly lower in the PCOS group compared to those in women with infertility due to male factor. Metformin therapy in PCOS patients preceding IVF cycles increased serum levels of sFas and decreased follicular fluid levels of sFasL compared to those on placebo. Follicular fluid from PCOS patients demonstrated luteinized granulosa cell DNA fragmentation in agarose gel, whereas a similar pattern was not observed among PCOS patients undergoing metformin therapy. CONCLUSION: Decreased serum levels of sFas and luteinized granulosa cell DNA fragmentation is observed in patients with PCOS undergoing IVF cycles. Metformin therapy preceding IVF demonstrates an antiapoptotic effect with increased serum levels of sFas, decreased follicular fluid levels of sFasL and prevention of luteinized granulosa cell DNA fragmentation.

Adult↗

PubMed1996

Serum levels of the soluble low affinity receptor for IgE and soluble interleukin-2 receptor in childhood, and their relation to age, gender, atopy and allergic disease.

Identifying immune factors associated with the development of atopy can enhance our understanding of the in vivo mechanisms involved and may have utility in paradigms designed to prevent disease. Two candidates suggested for such roles are the soluble low affinity receptor for IgE (sCD23) and the soluble interleukin-2 receptor (sCD25). To assess serum levels of these factors blood samples were collected at birth and at age 6 in a large nonselected population from Tucson, AZ. Log mean sCD23 and sCD25 levels decreased from birth to age 6, (for sCD23 0.60 ffi 0.26pg/l, n = 340 and 0.53 + 0.28pg/l, n = 333 and for sCD25 1.95 i 0.14pM, n = 304 and 1.86 ffi 0.20pM, n = 327, for the two ages respectively. Anglo children had lower sCD23 levels at birth compared to Hispanic children (p < 0.01); no effect of gender was observed. Skin test reactivity at age 6 was directly related to sCD25 levels at age 6 (p = 0.007) and even levels at birth showed a similar trend (p = 0.06). These relations were distinct from any relation to total serum IgE. No relation was observed with sCD23 levels for either skin test reactivity or serum IgE. The prevalences of asthma, rhinitis and eczema by age 6 were unrelated to sCD25 or sCD23 levels. The results indicate that soluble CD23 and CD25 have higher levels at birth than later in childhood and that the development of skin test reactivity may be associated with regulatory mechanisms involving sCD25, whereas sCD23 was not similarly implicated.

Age Factors↗

PubMed2002

Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and the development of symptomatic peripheral arterial disease in men.

BACKGROUND: Elevated levels of soluble cellular adhesion molecules have been linked to the development of occlusive coronary events in otherwise healthy individuals. It is not certain, however, whether similar relationships exist for the development of early systemic atherosclerosis. METHODS AND RESULTS: In a prospective, nested case-control study conducted among 14 916 middle-aged men, we evaluated the relationship between baseline levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and the subsequent development of symptomatic peripheral arterial disease (PAD) during a 9-year follow-up period. Median levels of sICAM-1 but not sVCAM-1 were significantly higher at baseline among men who developed PAD than among those who did not (285.2 versus 267.8 ng/mL [P=0.005] for sICAM-1 and 701.0 versus 709.3 ng/mL [P=0.8] for sVCAM-1). In analyses adjusted for age and smoking, the odds ratio in the highest compared with the lowest quartile of sICAM-1 was 3.9 (95% CI 1.7 to 8.6; P(trend)=0.001). After additional adjustment for lipid and nonlipid risk factors, including C-reactive protein, elevated sICAM-1 remained significantly associated with subsequent PAD (OR 3.5, 95% CI 1.4 to 8.5, P(trend)=0.008). Whereas a monotonic dose-response relationship was evident over the full spectrum of ICAM-1 levels, elevated sVCAM-1 was not associated with future PAD in either age- and smoking-adjusted or fully adjusted models. CONCLUSIONS: Elevated levels of sICAM-1 are independently associated with the development of accelerated atherosclerosis among otherwise healthy men even in the absence of acute coronary occlusion.

Adult↗

PubMedDate not supplied

Serum levels of soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in liver disease, and their changes by treatment with interferon.

Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured by an enzyme-linked immunosorbent assay in patients with chronic hepatitis (n = 57), liver cirrhosis (n = 19) and hepatocellular carcinoma (n = 33). Serum levels of sICAM-1 and sVCAM-1 were significantly higher in liver disease than those in controls (P < 0.0001 and P < 0.0005, respectively). A total of 22 patients with chronic hepatitis C were treated with interferon. Pretreatment levels of sICAM-1 and sVCAM-1 were not significantly different between complete responders and non-responders. In complete responders, serum sICAM-1 and sVCAM-1 levels 1 year after interferon treatment significantly decreased compared to the pretreatment levels (P < 0.005 and P < 0.05, respectively). Post-treatment levels of sICAM-1 and sVCAM-1 in complete responders were also significantly lower than those in non-responders (P < 0.005 and P < 0.05, respectively). This suggests that monitoring soluble adhesion molecules might be useful in the follow-up of patients with liver disease.

Adult↗

PubMed2000

A soluble lymphocyte activation gene-3 molecule used as a vaccine adjuvant elicits greater humoral and cellular immune responses to both particulate and soluble antigens.

The lymphocyte activation gene-3 (LAG-3) product is a MHC class II ligand that has been used in vivo to stimulate MHC class II+ APCs to increase tumor-specific immune responses. We investigated whether LAG-3 could also play an adjuvant role in vivo for the induction of humoral and CD4 or CD8 cell-mediated immune responses when immunizing mice with a particulate (hepatitis B surface Ag) or soluble (OVA) Ag. In both cases, coadministration of 1 microg of a soluble fusion protein between murine LAG-3 and the Fc fraction of a murine IgG2a mAb (mLAG-3Ig) as a vaccine adjuvant induced or increased CTL responses to the corresponding MHC class I-restricted peptide. In addition, splenocytes of mice vaccinated with either the particulate or soluble Ag plus mLAG-3Ig exhibited a significantly greater proliferative response than did splenocytes of mice immunized with Ag and a control Ig molecule. Similarly, these splenocytes had a greater Th1- but not Th2-type cytokine response. Finally, mice immunized with Ag plus mLAG-3Ig produced higher titers of Abs than mice immunized with Ag and a control Ig molecule. Thus, these data provide evidence of a novel means of improving the immunogenicity of subunit vaccines.

Adjuvants, Immunologic↗

PubMed1981

Soluble suppressor supernatants elaborated by concanavalin A-activated human mononuclear cells. I. Characterization of a soluble suppressor T cell proliferation.

When activated with the mitogenic lectin, concanavalin A, a subset of human peripheral blood mononuclear cells differentiate into potent suppressor cells that negatively modulate both cellular and humoral immune reactions. In addition to inhibitory cell-cell interactions, these regulatory cells elaborate a soluble immune suppressor supernatant (SISS) containing at lest 2 distinct suppressor factors. One of these factors, SISS-T, inhibits mitogen- and antigen-stimulated T cell proliferation, whereas the other, SISS-B, inhibits B cell immunoglobulin production. Characteristics of the latter inhibitor are reported in the companion paper. Properties of the soluble suppressor of T cell proliferation (SISS-T) include: 1) a m.w. of 30 to 45,000, 2) inhibition by a noncytotoxic mechanism, 3) instability at 56 degrees C, 4) loss of activity in the presence of the monosaccharide N-acetyl-D-glucosamine and retention on N-acetyl-D-glucosamine affinity columns, 5) binding to the same surface glycoprotein receptors recognized by the lectins wheat germ agglutinin and Agaricus bisporus lectin, which produce similar inhibition of mitogen- or antigen-induced lymphocyte proliferation, 6) elaboration by cells irradiated with 500 and 2000 R but not 6000 R, 7) a minimum requirement for 24 hr of lectin stimulation for production, and 8) elaboration by adherent cells or alternatively cellular collaboration requiring the participation of adherent cells. These data indicate that human suppressor cells are capable of modulating T cell function via the production of a soluble saccharide-specific factor(s) that interacts with defined surface glycoprotein or glycolipid receptors. These same receptors recognized by the suppressive endogenous lectin are also activated by selected exogenous nonmitogenic lectins that produce similar inhibition of T cell metabolism.

Acetylgalactosamine↗

PubMed1981

Soluble suppressor supernatants elaborated by concanavalin A-activated human mononuclear cells. II. Characterization of a soluble suppressor of B cell immunoglobulin production.

Human peripheral blood mononuclear cells (PBMC) activated with the mitogenic lectin concanavalin A (Con A) elaborate a soluble immune suppressor supernatant (SISS) that contains at least 2 distinct suppressor factors. One of these, SISS-B, inhibits polyclonal B cell immunoglobulin production whereas the other, SISS-T, suppresses T cell proliferation to both mitogens and antigens. The latter mediator is discussed in the companion paper. Characteristics of the human soluble suppressor of B cell immunoglobulin production (SISS-B) include: 1) inhibition by a noncytotoxic mechanism, 2) loss of activity in the presence of the monosaccharide L-rhamnose, 3) appearance within 8 to 16 hr after the addition of Con A, 4) elaboration by cells irradiated with 500 or 2000 rads, 5) production by highly purified T cells, 6) stability at pH 2.5 but instability at 56 degrees C, and 7) m.w. of 60 to 80,000. These data indicate that after Con A activation, selected T cells not only become potent suppressor cells, but also generate a soluble saccharide-specific factor(s) that inhibits polyclonal immunoglobulin production by human B cells.

Acetylglucosamine↗

PubMed1995

Modulation of cell-bound and soluble CD23, spontaneous and ongoing IgE synthesis of human peripheral blood mononuclear cells by soluble IL-4 receptors and the partial antagonistic IL-4 mutant protein IL-4 (Y124D).

We studied the influence of human recombinant soluble interleukin-4 receptors (sIL-4R) and a partial antagonistic mutant IL-4 protein, IL-4(Y124D), on the in vitro CD23 expression, soluble (s)CD23 release and IgE synthesis of human peripheral blood mononuclear cells (PBMC). The data show that sIL-4R suppressed the IL-4-induced IgE synthesis of PBMC. sIL-4R fusion protein stabilized with human Fc gamma fragments showed a more pronounced effect than unconjugated sIL-4R. IL-4(Y124D) also suppressed the IL-4-induced IgE synthesis. The IL-4-induced antigen CD23 and its soluble fragments were suppressed by sIL-4R and IL-4(Y124D). PBMC of atopic donors with a spontaneous in vitro IgE synthesis showed a partial suppression of the IgE production after sIL-4R or IL-4(Y124D) application. The IgE synthesis and sCD23 release of normal donor PBMC were suppressed when the substances were applied 0-4 days after IL-4 treatment. After 4 days of IL-4 stimulation, sIL-4R and IL-4(Y124D) enhanced the IgE synthesis. These data demonstrate that sIL-4R and IL-4(Y124D) are suppressive for the primary IgE synthesis induced by IL-4. In contrast, the ongoing IgE synthesis was only partially modulated by sIL-4R and IL-4(Y124D), and in some conditions even an enhancement of the IgE production was observed. These data suggest a differential function for IL-4 in the early and late phase of PBMC IgE production.

Adult↗

PubMed1994

[Immunological findings of bronchoalveolar lavage fluid (BALF) in sarcoidosis; analysis of soluble CD4 molecule and soluble CD8 molecule].

Since the introduction of bronchoalveolar lavage (BAL) by Reynolds and Newball in 1974, this procedure has been used to characterize the cellular and soluble components of alveolar lining fluid in many interstitial lung diseases. We reviewed BAL fluid findings of clinical and pathophysiologic researches in patients with pulmonary sarcoidosis. Moreover, our recent data about soluble CD4 molecule (sCD4) and soluble CD8 molecule (sCD8) were also described. The sarcoidosis patients had the significantly higher level of sCD4 in BAL fluid compared with normal subjects. The level of sCD8 in serum in active sarcoidosis was significantly higher than that in normal subjects. Furthermore, significant correlation between the levels of serum sCD8 and ACE was observed in sarcoidosis.

Adult↗

PubMed1994

[Levels of soluble CD4 and soluble CD8 in patients with sarcoidosis].

Levels of soluble CD4 (sCD4) and soluble CD8 (sCD8) in serum and bronchoalveolar lavage fluid (BALF) were determined in 36 patients with sarcoidosis and 20 healthy controls by an ELISA method. In addition, the possible sources of sCD4 and sCD8 were examined in detail. The sCD4 levels in serum did not differ significantly between sarcoidosis patients and controls. The sCD8 levels in the sera of sarcoidosis patients with a high serum angiotensin-converting enzyme (ACE) level were significantly higher than those of patients with a normal serum ACE level (413 +/- 148 U/ml vs. 297 +/- 76 U/ml, p < 0.01). The high ACE group also had significantly increased serum sCD8 levels as compared to controls (323 +/- 111 U/ml, p < 0.05). In the sarcoidosis patients, the mean serum sCD8 level was 308 +/- 46 U/ml in stage 0, 339 +/- 107 U/ml in stage I, 557 +/- 141 U/ml in stage II, and 474 +/- 211 U/ml in stage III. The stage II group had a significantly higher sCD8 level than either the stage 0 or I groups (p < 0.05). In the sarcoidosis patients, the sCD8 level correlated significantly with the level of either ACE or soluble Interleukin-2 receptor in serum (p < 0.05). The sCD4 level in BALF was significantly higher in sarcoidosis patients than in controls (4.10 +/- 1.90 U/ml vs. 2.39 +/- 0.12 U/ml, p < 0.01), while the sCD8 level in BALF tended to be higher in sarcoidosis patients than in controls (4.31 +/- 4.39 U/ml vs. 2.02 +/- 1.52 U/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1998

Soluble IL-6 receptor potentiates the antagonistic activity of soluble gp130 on IL-6 responses.

Soluble receptors for several cytokines have been detected in body fluids and are believed to modulate the cytokine response by binding the ligand and thereby reducing its bioavailability. In the case of IL-6, the situation is more complex. The receptor consists of two components, including a ligand-binding alpha-subunit (IL-6R, gp80, or CD126), which in its soluble (s) form (sIL-6R) acts agonistically by making the ligand accessible to the second subunit, the signal transducer gp130 (CD130). Soluble forms of both receptor subunits are present in human blood. Gel filtration of iodinated IL-6 that had been incubated with human serum revealed that IL-6 is partially trapped in IL-6/sIL-6R/sgp130 ternary complexes. sgp130 from human plasma was enriched by immunoaffinity chromatography and identified as a 100-kDa protein. Functionally equivalent rsgp130 was produced in baculovirus-infected insect cells to study its antagonistic potential on four different cell types. It was found that in situations in which cells lacking membrane-bound IL-6R were stimulated with IL-6/sIL-6R complexes, sgp130 was a much more potent antagonist than it was on IL-6R-positive cells stimulated with IL-6 alone. In the latter case, the neutralizing activity of sgp130 could be markedly enhanced by addition of sIL-6R. As a consequence of these findings, sIL-6R of human plasma must be regarded as an antagonistic molecule that enhances the inhibitory activity of sgp130. Furthermore, in combination with sIL-6R, sgp130 is a promising candidate for the development of IL-6 antagonists.

Adjuvants, Immunologic↗

PubMed2001

Optimizing therapeutic strategies to inhibit circulating soluble target molecules with monoclonal antibodies: example of the soluble IL-6 receptors.

Therapeutic targeting of soluble molecules such as cytokines can be achieved with monoclonal antibodies (mAb). Anti-IL-6 mAb have been shown to form circulating complexes, resulting in the increase of the half-life of the cytokine in vivo. In IL-6-related diseases, the soluble human IL-6 receptors (shIL-6R), which have been shown to possess strong agonist activity, circulate in the plasma at a high concentration and must be neutralized. Their clearance was studied in mice that had been made to express circulating shIL-6R after i.p. grafting of mouse thymoma cells transfected with a gene coding for shIL-6R, treated with various anti-shIL-6R mAb recognizing different epitopes of the molecule. Injection of one anti-hIL-6R mAb stabilized the short-lived hIL-6R and led to their accumulation. The same result was observed when two mAb directed against two different epitopes of the hIL-6R were used. Clearance of the receptors was only achieved when three mAb specific for three different epitopes were injected. A permanent clearing of the hIL-6R could be obtained by repeated injections of the clearing mixture. No correlation was found between the ability of the mAb to clear the sIL-6R and to immunoprecipitate them in agarose gel. The F(ab')2 fragments lost the clearing ability of the intact mAb. These results clearly show that therapeutic clearance of sIL-6R by mAb need at least three mAb directed against three different epitopes of the molecule, a conclusion which is likely to apply for clearing any soluble target molecule.

Animals↗

PubMed2005

Influence of open versus laparoscopically assisted colectomy on soluble vascular endothelial growth factor (sVEGF) and its soluble receptor 1 (sVEGFR1).

INTRODUCTION: Minimal invasive colectomy may attenuate surgery-induced immunomodulation. This may in part be due to a reduced postoperative inflammation-mediated angiogenic stimulus directed by the proangiogenic factor VEGF and its neutralizing receptor VEGFR1. Thus, we evaluated perioperative plasma concentrations of soluble VEGF (sVEGF) and soluble VEGFR1 (sVEGFR1) in patients undergoing elective colectomy. METHODS: 60 consecutive patients were randomized to undergo laparoscopically assisted or open right or left sided colectomy. Blood samples were drawn preoperatively, intraoperatively and postoperatively until 30 days after the operation. Commercially available ELISA methods were used for determination of sVEGF and sVEGFR1. RESULTS: Patients with cancer (n = 48) had higher preoperative levels of sVEGF compared to patients with benign disease (n = 12) (p = 0.04), while there was no significant difference in sVEGFR1 levels (p = 0.053). Soluble VEGF (p < 0.0001) and sVEGFR1 (p < 0.0001) levels fluctuated intra- and postoperatively. However, the intra- and postoperative levels of sVEGF and sVEGFR1 were similar at all time points in patients undergoing laparoscopically assisted or open resection. CONCLUSION: Although significant fluctuation in sVEGF and sVEGFR1 concentrations during the perioperative period was shown, patients who underwent laparoscopically assisted resection had similar levels as patients who underwent open resection.

Aged↗

PubMed2000

Circulating soluble adhesion molecules in patients with systemic sclerosis: correlation between circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) and impaired left ventricular diastolic function.

The objective of this paper is to investigate the relation between circulating soluble adhesion molecules and cardiac involvement, as assessed by echocardiography in patients with systemic sclerosis (SSc). Nineteen patients with SSc were submitted for assessment of serum levels of circulating soluble intercellular adhesion molecules (sICAM-1), and soluble vascular cell adhesion molecules-1 (sVCAM-1), and echocardiography. Abnormal left ventricular filling patterns (down E/A ratio) were detected in ten patients (52.6%) with significant negative correlation with sVCAM-1 (r = -0.484, P < 0.05). It was also significantly correlated with age (r = -0.791, P < 0.01), age of onset (r = -0.468, P < 0.05), degree of dyspnea (r = -0.687, P < 0.01), and erythrocyte sedimentation rate (ESR) (r = -0.489, P < 0.05). Our findings suggest an important role for sVCAM-1 as a marker of disease severity and impaired left ventricular filling pattern in SSc.

Activities of Daily Living↗

PubMed2005

Inverse correlation between soluble CD40 ligand and soluble CD40 is absent in patients with unstable angina.

The CD40/CD40 ligand (CD40L) system mediates inflammatory processes important in atherogenesis and plaque instability. The expression of CD40L on activated T cells was suppressed by soluble CD40 (sCD40) in vitro. However, the relationship between soluble CD40L (sCD40L) and sCD40 in unstable angina (UA) is still unknown. Thirty-seven consecutive patients with recent chest pain or discomfort were recruited. Patients with both Braunwald's class IB-IIIB and with coronary stenosis (or stenoses) of >75% were assigned to the UA group (n = 19, aged 67.2 +/- 8.2 years), and the rest to the control group (n = 18, aged 63.4 +/- 8.7 years). The serum levels of sCD40L and sCD40, and the plasma levels of matrix metalloproteinase (MMP)-9, were measured by enzyme-linked immunosorbent assays. A significantly inverse correlation between sCD40L and sCD40 was shown in the controls (r = -0.72, P = 0.0007), but was absent in the UA group (r = -0.16, P not significant), although there was no statistical significance between these groups in terms of serum levels of sCD40L or sCD40. The difference of the regression slopes of these regression lines was statistically significant (P < 0.01). Additionally, there was a significant correlation between sCD40 and plasma levels of MMP-9 in the patients with and without UA (r = 0.58, P = 0.0096), but no significant correlation between sCD40L and MMP-9 levels (r = 0.00, P not significant). The balance between CD40 and CD40L may be lost in patients with UA. Soluble CD40 expression may also be related to MMP-9 expression in atherosclerotic tissues.

Aged↗

PubMed2005

Clinical significance of serum levels of soluble intercellular adhesion molecule-1 and soluble L-selectin in malignant melanoma.

Although several molecules have been evaluated as tumor markers of malignant melanoma (MM) progression, there are few available markers sensitive enough to detect recurrence or metastasis. The objective of the present study was to determine clinical significance of serum soluble adhesion molecules in the monitoring of progression in patients with MM. Serum levels of soluble L-selectin (sL-selectin), sE-selectin, sP-selectin, and soluble intercellular adhesion molecule-1 (sICAM-1) were determined by ELISA in 57 MM patients. In a retrospective longitudinal study, nine serum samples from two MM patients were analyzed during a follow-up period of 4.0 and 4.3 years, respectively. Serum sICAM-1 levels in MM patients were significantly higher than those in healthy controls and tended to be elevated as the disease stage progressed. In contrast, serum sL-selectin levels were significantly lower in MM patients compared to healthy controls and tended to decrease as the disease stage progressed. There was no significant difference in serum sE-selectin and sP-selectin levels between MM patients and normal control. In a longitudinal study, increased sICAM-1 and decreased sL-selectin levels were generally associated with the progression of MM. These results suggest that monitoring both sICAM-1 and sL-selectin is available to evaluate the progression of MM.

Biomarkers, Tumor↗

PubMed1996

Tumour necrosis factor (TNF) soluble receptors in malignant melanoma: correlation with soluble ICAM-1 levels.

It has been recently suggested that soluble tumour necrosis factor receptors (sTNF-Rs) may represent prognostic factors in cancer. In malignant melanoma, the intercellular adhesion molecule (ICAM-1) has been described as involved in progression of the disease and is upregulated by TNF alpha. We report in this study the serum concentrations of sTNF-R1 and sTNF-R2 in 32 patients with primary melanoma and in 21 patients with metastatic melanoma, in correlation with those of soluble ICAM-1 (sICAM-1). Significantly raised sTNF-R1 levels were detected only in patients with metastatic melanoma compared with normal controls (P < 0.002), whereas sTNF-R2 levels were increased both in primary and metastatic melanoma (P < 0.001). The ratio of type 2 to type 1 proteins increased in malignant melanoma compared with the controls but remained constant with the progression of the disease. A correlation between sTNF-Rs and sICAM-1 concentrations in patients' sera was observed in metastatic melanoma. The combined adverse effects of these soluble proteins on normal immune effector functions may contribute to tumour progression.

Adult↗