C-reactive protein and embolization during carotid artery stenting. A serological and morphological study.

INTRODUCTION: High-sensitivity C-Reactive Protein (hsCRP) levels are correlated with vulnerable carotid plaques, although their impact on the outcome of carotid revascularization is unknown. The aim of our study was to investigate the correlation between hsCRP and embolization during carotid artery stenting (CAS). METHODS: Patients with symptomatic carotid stenosis were submitted to CAS with distal protection filters. Serum hsCRP was analysed prior to CAS and patients were divided into two groups: Class I, patients presenting hsCRP < 5 mg/l and, Class II, patients presenting hsCRP≥5 mg/l. Plaques were categorised by ultrasound grey scale measurement as homogenous and dishomogenous. Afterwards CAS filters were analyzed microscopically and ultrastructurally to determine the type and the amount of debris present, based on percentage of surface involvement (SI) and pore occluded (PO) by embolic material. RESULTS: Fourteen patients underwent uneventful CAS, with a mean hsCRP of 11.5±18.4 mg/l. Eight patients were in Class I and six in Class II. All filters had microscopic debris. SI was 25.4% in Class I and 33.3% in Class II (p=ns), PO 22.9% and 33.3% respectively (p=0.049). Patients in Class II who also had a dishomogenous plaque showed greater SI and PO compared with patients in Class I with homogenous plaque (35.0% vs. 21.8% and 40.4% vs. 22.7% respectively, p<0.05). Microscopically embolic material was identified as atherosclerotic plaque fragments and platelet aggregates and was similar in both groups. DISCUSSION: High hsCRP levels are associated with significantly greater embolization during CAS in symptomatic patients, particularly in dishomogenous plaque. Although these results need further investigation due to the limited number of enrolled patients, this study suggests that CAS may not be indicated as a method of carotid revascularization in this setting.

The relationship between serum-soluble interleukin-2 receptor and radiological evolution in psoriatic arthritis patients treated with cyclosporin-A.

Aims of the study to evaluate the radiologically detected progression of joint damage in patients with psoriatic arthritis (PA) treated with cyclosporin-A (CsA) and to look for clinical and/or immunological parameters that might predict outcome. Twenty-four out-patients suffering from active PA entered a 2-year open prospective study on low-dose CsA (starting dose 3 mg/kg/day). Fifteen patients completed the study. Plain radiographs of hands and feet at study entry and at the end of follow-up were compared for the number of eroded joints. Serum-soluble IL-2 receptor (sIL-2R) levels were available in 13/15 patients before CsA therapy, after 6 months and after 2 years. The mean number of eroded joints per patient increased significantly during the study period (P = 0.017). Nine patients had less than two new eroded joints (responders) while the remaining six patients had five or more new eroded joints (non-responders). Serum sIL-2R levels were in the normal range after 6 months and 2 years of CsA treatment in all the responder patients and were above the 95th percentile of the control population in the six non-responders. We did not find any other demographical, clinical, radiological or laboratory parameter predictive of outcome in conclusion. (1) CsA seems to be able to control the 2-year progression of the radiologically measured damage in peripheral joints in 60% of PA patients. (2) A normal serum sIL-2R level after 6 months of therapy seems to have a prognostic value for a good outcome in PA patients treated with CsA.

T-helper 2 type cytokine and soluble interleukin-2 receptor levels in seminal plasma of infertile men.

PROBLEM: The role of cell-mediated immunity (CMI) in unexplained male infertility and impaired sperm function has been explored. METHOD OF STUDY: The presence of cytokines, namely, interleukin-4 (IL-4), interleukin-6 (IL-6), and the soluble interleukin-2 receptor (SIL-2R), was investigated in seminal plasma of 18 fertile and 20 infertile subjects, using specific enzyme-linked immunoadsorbent assays. RESULTS: IL-4 was not detected. SIL-2R was detected, but the concentration difference between the fertile and infertile group was not significant. IL-6 was detected with significantly higher levels in the infertile group compared to the fertile group. IL-6 levels in seminal plasma correlated positively with leukocyte count and negatively with sperm count, motility, and morphology. CONCLUSIONS: These findings show: a) a lack of IL-4 in seminal plasma; b) similar SIL-2R levels in fertile and infertile seminal plasma; c) increased IL-6 secretion in seminal plasma of infertile subjects; and d) specific correlations of IL-6 with the main semen parameters.

Impaired lymphocyte proliferation in human acute pancreatitis.

PURPOSE: We evaluated the proliferative response of lymphocytes to phytohemagglutinin P (PHA P), concanavalin A (Con A), and pokeweed mitogen (PWM) during the course of acute pancreatitis. PATIENTS AND METHODS: Sixty consecutive patients with acute pancreatitis were studied within 48 h of the onset of pain, and 16 of them were also studied 1 month after complete recovery. According to the Atlanta criteria, 21 patients had severe disease and 39 had mild disease. Fifteen healthy subjects and 11 patients with nonpancreatic acute abdomen were studied as controls. In 12 patients with acute pancreatitis the lymphocyte proliferation after stimulation with the three mitogens was also assessed in autologous and heterologous plasma. RESULTS: The lymphocyte proliferative response to optimal doses of PHA P, Con A, and PWM was significantly lower (p < 0.001) in acute pancreatitis patients (mean +/- SD; PHA P 74,310 +/- 22,960 cpm; Con A 64,669 +/- 20,188 cpm; PWM 26,714 +/- 6,436 cpm) than in healthy subjects (PHA P 111,316 +/- 12,044 cpm; Con A 96,276 +/- 12,327 cpm; PWM 33,957 +/- 3,601 cpm). Patients with nonpancreatic acute abdomen had a significantly higher lymphocyte proliferative response to PHA P and Con A than acute pancreatitis patients (PHA P p < 0.002; Con A p < 0.01; PHA P 91,116 +/- 22,995 cpm; Con A 77,879 +/- 19,083 cpm). In patients with acute pancreatitis, lymphocyte proliferation stimulated with PHA P and Con A was significantly lower (PHA P p < 0.005; Con A p < 0.001) in those with severe disease (PHA P 63,190 +/- 15,157 cpm; Con A 52,813 +/- 13,324 cpm) than in those with mild disease (PHA P 80,298 +/- 24,340 cpm; Con A 71,052 +/- 20,490 cpm). In the group of 16 patients studied during the initial phase of acute pancreatitis and 1 month after recovery, lymphocyte proliferation significantly improved after remission of the disease but remained impaired compared with that of healthy subjects. No difference was found in the lymphocyte proliferation of the 12 patients with acute pancreatitis assayed in autologous and heterologous plasma. CONCLUSIONS: The peripheral lymphocyte proliferative response to mitogen stimulation in patients with acute pancreatitis was decreased during the early phases of the disease.

CD8 lymphocyte subsets in active polymyalgia rheumatica: comparison with elderly-onset and adult rheumatoid arthritis and influence of prednisone therapy.

The aim of this study was to evaluate CD8 lymphocyte subsets in active polymyalgia rheumatica (PMR), to determine whether low percentages of CD8+ cells could be used to differentiate PMR from elderly-onset (EORA) and adult rheumatoid arthritis (RA), and to investigate the effects of prednisone on CD8 lymphocyte subsets. A significant reduction of percentages and absolute numbers of CD8bright+ cells was observed in patients with active PMR. Both CD8bright+, CD57- and CD8bright+, CD57+ subsets were significantly reduced. Reduced percentages of CD8+ cells were observed in 55% of patients with active PMR/giant cell arteritis (GCA), in 23% with EORA and in 44% with adult RA. Prednisone therapy in PMR patients, after only 1 week, increased the lymphocyte count and the absolute numbers of lymphocyte subsets significantly. However, the percentages of CD8bright+ cells remained persistently low for the 2 yr study period in 80% of the patients with low pre-treatment levels. Our results demonstrate that CD8 cell percentage is a poor epidemiological discriminator for PMR diagnosis. Notwithstanding the rise in absolute numbers of CD8 cell subsets induced by prednisone, the persistently low percentages of CD8+ cells in a group of PMR patients indicate an abnormality connected with the disease.

Role of peripheral CD8 lymphocytes and soluble IL-2 receptor in predicting the duration of corticosteroid treatment in polymyalgia rheumatica and giant cell arteritis.

OBJECTIVES: To determine if the presence of low percentages of CD8 positive cells or high levels of soluble interleukin-2 receptors (sIL-2R) define a subgroup of patients with more severe polymyalgia rheumatica and giant cell arteritis (PMR/GCA). METHODS: 38 PMR/GCA patients were followed up prospectively. Serum levels of sIL-2R and peripheral blood CD8 lymphocytes were measured before the start of corticosteroid treatment, after six months of treatment and at the last visit. Phenotypical analysis of lymphocyte subpopulations was performed with a two colour technique, and assay of sIL-2R was performed using an enzyme-linked immunosorbent kit. Forty four healthy people matched for age and gender comprised a healthy control group. RESULTS: The median duration of follow up was 28 months (range 7-65). Corticosteroid treatment lasted a median of 23.5 months (7-65). Eleven patients (29%) were in remission at the end of follow up; 45% of the patients had at least one relapse or recurrence. Compared with controls, patients with active disease had a significantly lower percentage of CD8 cells and significantly increased sIL-2R levels. Erythrocyte sedimentation rate, C reactive protein, and sIL-2R values were significantly less after six months of steroid treatment compared with before treatment. The percentage of CD8 cells remained significantly lower at six months and the end of follow up compared with controls, while sIL-2R levels remained significantly greater. Patients in whom the percentage of CD8 cells at six months was lower than one SD of the mean of normal controls (26%) had a significantly longer duration of corticosteroid treatment, a greater cumulative dose of prednisone and more relapses or recurrences compared with patients in whom the percentage was in the normal range. The duration of treatment and the cumulative dose of prednisone were not influenced by the percentage of CD8 cells before treatment therapy or by the levels of sIL-2R after six months of treatment. CONCLUSIONS: A reduced percentage of CD8 cells after six months of treatment may be a useful outcome parameter which would identify a group of PMR/GCA patients likely to experience more severe disease, defined as longer duration of corticosteroid treatment, higher cumulative dose of prednisone, and relapse or recurrence of disease.

Circulating lymphocyte subsets in human acute pancreatitis.

We investigated peripheral lymphocyte subsets in 34 consecutive acute pancreatitis patients (21 males, 13 females; mean age, 57 years; range, 16-85 years) studied within 48 h of pain onset and for 5 consecutive days to understand better the immunological response during the course of the disease. The diagnosis was based on characteristic abdominal pain associated with a twofold increase in serum lipase and confirmed by imaging techniques in all patients. Acute pancreatitis was of biliary origin in 25 patients, due to alcohol abuse in 5, due to pancreas divisum in 1, and of unknown origin in 3. Fifteen patients had severe illness and 19 had mild disease. In all patients, total lymphocyte and lymphocyte subset counts were carried out on admission, as well as on the third and fifth day of hospitalization, using a flow cytometric analysis. Twenty-three patients (13 with severe illness and 10 with mild disease) also had a repeat count 1 month after recovery. Twenty-five healthy subjects and 27 patients with nonpancreatic acute abdomen comparable for sex and age were studied as controls. On the first day of the study, the leukocyte number was significantly higher in patients with acute pancreatitis and in those with nonpancreatic acute abdomen with respect to healthy subjects, whereas the number of total and CD4+, CD8+, CD3+ DR-, and CD3- DR+ lymphocytes was significantly lower in acute pancreatitis patients than in healthy subjects or in patients with nonpancreatic acute abdomen. These subject counts persisted on the third and fifth days of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum beta 2-microglobulin in chronic diseases of the pancreas.

Elevated serum concentrations of beta 2-Microglobulin (beta 2-MG) has been reported in a variety of chronic diseases and solid tumors. We determined serum beta 2-MG concentrations in 140 subjects divided into five groups: group 1, 34 patients with proven chronic pancreatitis, 8 of whom were studied during a painful relapse; group 2, 40 patients with pancreatic cancer staged according to the Cubilla-Fitzgerald classification; group 3, 40 healthy subjects; group 4, 10 patients with digestive nonpancreatic carcinomas; group 5, 16 patients with benign digestive nonpancreatic diseases. Serum soluble interleukin-2 receptor (sIL-2R) was also determined in all patients with pancreatic diseases as an index of immune system activation. In addition, serum CA 19-9 was assayed in patients of groups 2 and 4, and C-reactive protein (CRP) of groups 1 and 5. Renal function, evaluated by serum creatinine determination, was normal in all subjects studied. Patients with pancreatic cancer and those with chronic pancreatitis had serum concentrations of beta 2-MG significantly higher than those of healthy subjects (p < 0.001 and p < 0.005, respectively). Patients with stage I and stage III pancreatic cancer had similar serum levels of beta 2-MG, and these concentrations were significantly lower than those of patients with stage II tumors (p < 0.002 and p < 0.05, respectively). In chronic pancreatitis patients, those studied during painful relapse of the disease had serum concentrations of beta 2-MG similar to those studied during clinical remission.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell adhesion molecules CD11a and CD18 in blood monocytes in old age and the consequences for immunological dysfunction. Preliminary results.

Adhesion molecules, such as leukocyte-function-associated antigen (LFA-1 or CD11a/CD18), intercellular adhesion molecule 1 (ICAM-1 or CD54) and Hermes antigen (HCAM or CD44), have important roles in many adhesive interactions involving cells of the immune system. Since it has been shown that many immunological alterations were present in aged subjects, we studied the expression and density of these molecules on peripheral blood lymphocytes and monocytes from healthy old subjects. A decrease in monocyte subpopulations bearing CD11a/CD18 and an increase in CD11a/CD18 and and CD44 antigen density on lymphocytes and on monocytes, respectively, were observed. These changes might be an event in the mechanism leading to the decreased lymphocyte proliferative response in vitro and to other immunological dysfunctions reported in old subjects.

Serum soluble CD4 and CD8 levels in polymyalgia rheumatica.

OBJECTIVE: Soluble CD4 (sCD4) and sCD8 were measured in the sera of 19 patients with active polymyalgia rheumatica (PMR). METHODS: We correlated the results obtained with lymphocyte subpopulations, soluble interleukin 2 receptors (sIL-2R), and clinical and laboratory variables at diagnosis. In addition 15 patients were prospectively studied during a 6 month period of prednisone therapy. Assays of the sCD4 and sCD8 molecules and of the sIL-2R were performed using an enzyme-linked immunosorbent kit. RESULTS: Serum sCD8 and sIL-2R levels were significantly elevated in patients with active disease compared to normal controls, while serum sCD4 and the relative percentage of CD8+ T cell levels decreased. In the 15 patients prospectively studied sCD8 levels fell significantly after 1 week of therapy along with the remission of clinical disease and normalization of erythrocyte sedimentation rate. At the end of the study period, sCD8 values did not differ from normal controls and they were significantly reduced compared to baseline values. CD8+ lymphopenia persisted at the end of the study. sCD4 levels remained significantly lower during the study period. sIL-2R levels fell significantly at the end of the study period. However, the 6-month levels of sIL-2R remained significantly higher compared to controls. CONCLUSION: The rise of serum sCD8 levels observed in patients with PMR with active disease suggests an early activation of CD8 T cells. The therapeutic effect of steroid in PMR may be partially mediated by its effect on CD8 activated cells.

Serum soluble interleukin-2 receptor levels in rheumatoid arthritis: correlation with clinical and immunological parameters and with the response to auranofin treatment.

OBJECTIVE: 38 untreated patients suffering from rheumatoid arthritis (RA) were studied to evaluate the relationship between serum sIL-2R levels and laboratory and clinical indexes of disease activity and circulating lymphocyte subpopulations. Furthermore, we serially analyzed the correlation between the clinical response to oral gold (Auranofin) treatment and serum sIL-2R levels in 28 RA patients. METHODS: Patients received a complete rheumatological examination at entry and every 3 months during the study. A complete biochemical analysis was executed every month. Serum sIL-2R levels were evaluated before entering and at the 3rd and 6th month by ELISA: Phenotype analysis of peripheral blood mononuclear cells was performed by a two-color technique using the association of specific monoclonal antibodies. Samples were analyzed by a FACS-scan 440 cytofluorimeter with a single Argonion laser. RESULTS: Serum sIL-2R were significantly higher in RA patients than in controls and had a significant negative correlation with disease duration and a positive correlation with serum IgG and C3 levels. A significant positive correlation was found between serum sIL-2R levels and circulating CD3 + HLADR+, CD3-HLADR+ and CD20 + CD5-cells. After 6 months of auranofin therapy no differences in serum sIL-2R in comparison with basal levels were found in either responders or in non-responders. CONCLUSION: Serum sIL-2R level is not a good index of activity in RA patients and is not a useful marker of response to AU therapy.

Serum soluble interleukin-2 receptor in pancreatic cancer and chronic pancreatitis.

Activated lymphocytes can release a soluble form of interleukin-2 receptor (sIL-2R) and abnormally high serum levels of sIL-2R have been reported in patients with advanced solid tumours and in those with chronic disease. We determined serum sIL-2R concentrations in 34 patients with chronic pancreatitis (8 in painful relapse), in 40 with pancreatic tumours in various stages, and in 40 healthy subjects as controls. Patients with pancreatic cancer and those with chronic pancreatitis had significantly higher serum concentrations of sIL-2R than healthy subjects (p < 0.001). In patients with Stage II pancreatic cancer, serum levels of soluble receptors were similar to those in patients with Stage III tumours, and these concentrations were significantly higher than in patients with resectable cancer (p < 0.01 and p < 0.05, respectively). In chronic pancreatitis patients, those studied during painful relapse of the disease had higher serum concentrations of sIL-2R than those studied during clinical remission (p < 0.05). The results of our study suggest an activation of the cellular immune system in pancreatic cancer and in chronic pancreatitis.

Oral zinc supplementation in Down's syndrome subjects decreased infections and normalized some humoral and cellular immune parameters.

The effect of 4 months of oral zinc supplementation on immune functions in non-institutionalized young female and male Down's syndrome (DS) subjects was studied. Along with plasma levels of zinc, the immune parameters, measured before and after zinc treatment, were plasma levels of thymulin, the percentage and the absolute number of circulating white blood cells, total lymphocytes, lymphocyte subpopulations, the mitogen-induced lymphocyte proliferation, the production of interleukin-2, and the activity of stimulated granulocytes. Some immune parameters were significantly influenced by zinc treatment. In particular, a normalization of thymulin and zinc plasma levels were found in these subjects after zinc supplementation. At the end of the clinical trial, in vitro lymphocyte proliferation and polymorphonuclear activity also increased and reached normal values. Zinc administration exerted a positive clinical effect in these children, since a reduced incidence of infections was found.

Behavior of serum soluble interleukin-2 receptor, soluble CD8 and soluble CD4 in the early phases of acute pancreatitis.

When activated, lymphocytes secrete glycoproteins related to particular surface proteins, including soluble forms of the interleukin-2 receptor (sIL-2R) and of the surface proteins CD4 (sCD4) and CD8 (sCD8). We evaluated the release of these glycoproteins in order to assess the activation of the cellular immune system during the course of acute pancreatitis. Thirty-five patients with acute pancreatitis (22 M, 13 F, mean age 64 years, range 16-97) were studied. The diagnosis was based on typical abdominal pain associated with a twofold increase of serum lipase as well as morphological abnormalities compatible with acute pancreatitis seen at computed tomography and/or ultrasonography. The pancreatitis was of biliary origin in 22 patients, due to alcohol abuse in 8, due to pancreas divisum in 1, due to type IV hyperlipoproteinemia in 1 and of unknown origin in 3. Based on clinical outcome, 22 patients had mild pancreatitis, whereas 13 had severe disease. In all patients serum sIL-2R, sCD4 and sCD8 were determined on admission and daily for the following 5 days using enzyme immunoassay (EIA) techniques. Serum concentrations of sIL-2R and sCD8 were significantly higher in acute pancreatitis patients relative to healthy controls during the entire observation period, whereas sCD4 levels were significantly lower in acute pancreatitis patients than in the control group from the 2nd to the 6th day of observation. Serum sIL-2R concentrations were significantly higher in patients with severe pancreatitis than in those with the mild form of the disease, whereas no differences in serum concentrations of sCD8 and sCD4 were found between patients with mild pancreatitis and those with severe disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasmic levels of trace elements and immune functions in the healthy elderly.

Healthy elderly persons were selected according to an admission protocol which included clinical, hematological and biochemical parameters. Plasmic levels of zinc in these subjects were in the normal range, while plasmic copper was higher than that of young controls. The number of circulating lymphocytes and CD3+ cells was decreased; however, the absolute number of CD4+, CD8b, CD8d, CD20+ and CD57+ cells did not differ from that of controls. A decreased lymphocyte response to PHA in serum-free medium cultures was also observed in the healthy elderly persons.

Lymphocyte subpopulations analysis in peripheral blood in polymyalgia rheumatica/giant cell arteritis.

The phenotypic characteristics of peripheral blood lymphocytes were investigated in 22 patients suffering from active polymyalgia rheumatica/giant cell arteritis (PMR/GCA) prior to steroid treatment. We observed a significant reduction in the absolute number and the relative percentage of CD4-, CD8+ and CD3+, CD16+ and/or CD56+ cells compared to controls. Fifteen patients were investigated prospectively over a 6-month period of prednisone therapy. At the end of the study CD4-CD8+ cells had increased significantly compared to baselines, CD3+ CD16+ and/or CD56+ cells remained significantly lower when compared to controls. We did not observe any abnormalities in the absolute number and percentage of HLA-DR+ T lymphocytes, CD5+ B cells and NK cell phenotypes before or during steroid treatment. Our study confirms that there was significant increase in the absolute number of CD8+ T cells during steroid treatment in the PMR/GCA patients, but indicates the persistence of an immunological alteration despite the control of disease manifestations.

Immunologic effects in patients with psoriatic arthritis treated with cyclosporine A.

Twelve patients with psoriatic arthritis (PsA) and very active articular disease resistant to conventional second line therapy entered into a 6-month open study of cyclosporine A (CsA) at a starting dosage of 3 mg/kg/day. Comparisons of phenotypic characteristics of lymphocytes and response to mitogens of peripheral blood mononuclear cells (PBMC) were made between these patients with PsA before CsA therapy, 7 patients without prior 2nd line therapy, 14 untreated patients with psoriasis alone, and 61 healthy controls. We confirmed a significant reduction of the basal percentage of CD8+ cells and an increase in the CD4/CD8 ratio in patients with PsA before CsA therapy compared to controls. These abnormalities were not present in patients with PsA without prior 2nd line therapy and in patients with psoriasis alone. Peripheral blood activated T cells (CD3+, HLA-DR+), natural killer (NK) (CD3-, CD16+ and/or CD56+), total B and CD5+ B cells were decreased only in patients with PsA before CsA therapy. The reduction of non-MHC restricted cytotoxicity T (CD3+, CD16+ and/or CD56+) was observed in all the 3 groups of patients compared to controls. After the 6 months of CsA therapy we observed a significant increase of CD3+, HLA-DR+, CD3+, CD16+ and/or CD56+, total B, and CD20+, CD5+ cells in the 11 patients with PsA compared to pretreatment values. Contrary to azathioprine, CsA does not impair the NK cell population which has a protective role against cancer and viral infections.

Soluble interleukin 2 receptors in polymyalgia rheumatica/giant cell arteritis. Clinical and laboratory correlations.

Serum levels of soluble interleukin 2 receptors (sIL-2R) were measured in 21 patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA) prior to steroid treatment. These levels were significantly elevated in patients with PMR/GCA compared with healthy controls (p = 0.002). A significantly longer duration of morning stiffness (p = 0.005) was observed in patients with a high concentration of sIL-2R. A significant correlation was observed at diagnosis between sIL-2R and erythrocyte sedimentation rate (ESR) (p = 0.01) and between ESR and C-reactive protein (CRP) (p = 0.005). We investigated prospectively a group of 10 patients over a period of 6 months of prednisone therapy. At the end of the study sIL-2R levels fell significantly compared to pretreatment values (p = 0.02), but remained significantly higher compared to controls (p = 0.02). ESR and CRP values also fell significantly compared to pretreatment levels (p = 0.0001 in both cases). We observed a significant correlation between the decrease in ESR values and the decrease in sIL-2R and CRP levels after 6 weeks (p = 0.01 in both cases) and after 6 months of therapy (p = 0.002 and p = 0.05). sIL-2R may be considered a useful serologic marker for monitoring response to steroid therapy in patients with PMR/GCA. This laboratory variable correlated more closely with ESR than with CRP. The presence of elevated levels of sIL-2R is likely to reflect T cell activation occurring in PMR/GCA. T lymphocyte activation persisted after 6 months of steroid therapy, despite rapid and continuous control of disease manifestations.

Lymphocyte release of soluble IL-2 receptors in patients with minimal change nephropathy.

Minimal change nephrotic syndrome has been reported to be a lymphocyte-mediated disorder. It has been suggested that the secretion of lymphokine(s) is involved in the pathogenesis of MCN and in determining proteinuria. The presence of a soluble form of IL-2 receptor (sIL-2R) has been previously described in the sera of patients with some autoimmune disorders. In this work, we report the detection of high sIL-2R levels, both in the plasma (mean value 844 +/- 436 U/ml versus normal value 276 +/- 86 U/ml) and urine of patients with MCN during the nephrotic phase alone. Instead, when the patients achieve stable remission, sIL-2R levels decrease to within normal values (mean value 332 +/- 272 U/ml). Furthermore, during the nephrotic syndrome we observed a significant inverse relationship between sIL-2R plasma levels and the mitogenic response to PHA (p less than 0.005). Since sIL-2R exerts a down-modulation on T-proliferative expansion, sIL-2R might represent one of the inhibitory serum factors extensively reported in the serum of patients with MCN-induced nephrotic syndrome.

Low dose cyclosporine A in psoriatic arthritis: relation between soluble interleukin 2 receptors and response to therapy.

Twelve patients with psoriatic arthritis (PsA) were treated with low doses of cyclosporine A (CsA) (the initial dose was 3 mg/kg daily) and were entered into an open 6-month study. At the end of the study arthritis was improved in 7 patients (number of patients achieving a 50% or more reduction in the number of swollen or tender joints) and unchanged in 4 patients. Cutaneous psoriasis also improved significantly as shown by psoriasis area and severity index score. Only one patient withdrew from the study after one month because of severe nephrotoxicity. Serum creatinine fell to baseline value 6 weeks after the discontinuation of CsA. Three patients had minor side effects. CsA maintained articular improvement also in the 9 patients who are still taking this drug (mean duration of therapy of 12 +/- 0.8 months). There was no significant reduction of erythrocyte sedimentation rate during the study period. We assayed levels of soluble interleukin 2 receptors (sIL-2R) in serial serum samples obtained from 10 patients during the study period. Concentrations of sIL-2R were significantly increased in patients with PsA compared to controls. In 6 responder patients we observed a parallel decrease in joint pain/tenderness score and serum sIL-2R values. This finding was not observed in 4 nonresponders. Our results suggest that low dose CsA is a short term effective and safe therapy in patients with PsA and that serial sIL-2R levels are a useful means of measuring changes in disease activity.