Serum Interleukin-2 Receptor Research Articles

Evidence of Abnormal Epidermal Nerve Fiber Density in Fibromyalgia: Clinical and Immunologic Implications

A subset of patients with fibromyalgia (FM) exhibit a large fiber demyelinating peripheral polyneuropathy akin to that seen in chronic inflammatory demyelinating polyneuropathy (CIDP). It has been suggested that this demyelinating process is likely to be immune mediated. Because it is known that similar large fiber neuropathic lesions may be associated with a cutaneous small fiber neuropathy, we sought to determine the prevalence of small fiber neuropathy, as measured by epidermal nerve fiber density (ENFD), in a series of patients with FM and clinically healthy control subjects. Forty-one consecutive patients with FM and 47 control subjects underwent a 3-mm punch skin biopsy at the proximal thigh and distal leg near the ankle, for analysis of the ENFD. Patients with FM who had clinical evidence of a disorder known to be associated with small fiber neuropathy were excluded. The patients with FM also underwent pinwheel testing and vibratory testing for hypesthesia and serologic testing for a series of cytokine, circulating immune complex, and complement measurements. All patients with FM had evidence of stocking hypesthesia. The ENFD of patients with FM was lower than that of control subjects at both the calf (mean ± SD 5.8 ± 2.8 versus 7.4 ± 1.9; P = 0.0002) and thigh (9.3 ± 3.2 versus 11.3 ± 2.0; P = 0.0007). There was an inverse correlation between calf ENFD and age at the time of skin biopsy in patients with FM (r = -0.29, P = 0.03) but not in control subjects; however, analysis of covariance showed that this relationship could not be explained by aging alone. Serologic evaluation showed an inverse correlation between calf ENFD in patients with FM and the interleukin-2 receptor (IL-2R) level (r = -0.28, P = 0.04). However, an inverse correlation between thigh ENFD and serum IL-2R levels did not reach significance (P = 0.08). Analysis of thigh-to-calf ENFD ratios suggested that the ENFD decline in FM is affected by both a diffuse and a length-dependent process. The calf and thigh ENFD in patients with FM is significantly diminished compared with that in control subjects. Advancing age alone cannot explain this finding. Calf ENFD was inversely correlated, although weakly, with serum levels of IL-2R. These findings suggest that small fiber neuropathy is likely to contribute to the pain symptoms of FM; that pain in this disorder arises, in part, from a peripheral immune-mediated process; and that measurement of ENFD may be a useful clinical tool in FM.

The interleukin-6 receptor Asp358Ala single nucleotide polymorphism rs2228145 confers increased proteolytic conversion rates by ADAM proteases

The pleiotropic activities of Interleukin (IL-)6 are controlled by membrane-bound and soluble forms of the IL-6 receptor (IL-6R) in processes called classic and trans-signaling, respectively. The coding single nucleotide polymorphism (SNP) rs2228145 of the Interleukin 6 receptor (IL-6R Asp358Ala variant) is associated with a 2-fold increase in soluble IL-6R (sIL-6R) serum levels resulting in reduced IL-6-induced C-reactive protein (CRP) production and a reduced risk for coronary heart disease. It was suggested that the increased sIL-6R level leads to decreased IL-6 classic or increased IL-6 trans-signaling. Irrespective of the functional outcome of increased sIL-6R serum level, it is still under debate, whether the increased sIL-6R serum levels emerged from differential splicing or ectodomain shedding. Here we show that increased proteolytic ectodomain shedding mediated by the A Disintegrin and metalloproteinase domain (ADAM) proteases ADAM10 and ADAM17 caused increased sIL-6R serum level in vitro as well as in healthy volunteers homozygous for the IL-6R Asp358Ala allele. Differential splicing of the IL-6R appears to have only a minor effect on sIL-6R level. Increased ectodomain shedding resulted in reduced cell-surface expression of the IL-6R Asp358Ala variant compared to the common IL-6R variant. In conclusion, increased IL-6R ectodomain shedding is a mechanistic explanation for the increased serum IL-6R levels found in persons homozygous for the rs2228145 IL-6R Asp358Ala variant.

The relationship between interleukin‐1 receptor antagonist and cognitive function in older adults with bipolar disorder

Cognitive impairments are a feature of bipolar disorder (BD) and could be worsened by inflammatory cytokines. We determined whether (i) serum interleukin-1 receptor antagonist (IL-1RA) was increased in elderly BD subjects; (ii) whether IL-1RA was associated with worse neurocognitive function; and (iii) whether IL-1RA was associated with white matter integrity. Twenty-one euthymic BD patients (65 +/- 9 years) with serum available for IL-1RA measures by enzyme-linked immunoassays were compared with 26 similarly aged control participants. Four factor analysis-derived z-scores and a global z-score were obtained from a battery of 21 neurocognitive tests. Diffusion tensor images were used to obtain fractional anisotropy (FA), and an automated labeling pathway algorithm was used to obtain white matter hyperintensity burden. Interleukin-1 receptor antagonist was elevated in BD subjects compared with controls (439+/-326 pg/mL vs. 269+/-109 pg/mL; p = 0.004). Moreover, IL-1RA was inversely correlated with three cognitive function factors and global cognition (r = -0.37; p = 0.01). IL-1RA continued to correlate with global cognitive function even when covarying for either IL-6 or brain-derived neurotrophic factor. Although FA was lower in BD subjects (0.368 +/- 0.02 vs. 0.381 +/- 0.01; p = 0.02), IL-1RA was not associated with FA or white matter hyperintensity burden. Elevated serum levels of IL-1RA in BD subjects, even during euthymic states, were associated with worse cognitive function. This association was not explained by co-occurring increases in IL-6, by decreased brain-derived neurotrophic factor, nor by measures of white matter integrity. These cross-sectional findings support the possibility that the IL-1 family may contribute to cognitive impairments in BD.

AB0771 Tocilizumab in patients with recent onset polymyalgia rheumatica (PMR) and contraindications to steroid use

BackgroundCorticosteroids (CS) are the drug of choice in treating polymyalgia rheumatica (PMR). However CS-related adverse events are frequently observed during treatment course. A previous report showed that tocilizumab (TCZ) is...

Impact of preoperative serum interleukin-2 receptor alpha levels on survival and its correlation with clinicopathological parameters in colorectal cancer

Impact of preoperative serum interleukin-2 receptor alpha levels on survival and its correlation with clinicopathological parameters in colorectal cancer

Utility of Serum Neopterin and Serum IL-2 Receptor Levels to Predict Absolute CD4 T Lymphocyte Count in HIV Infected Cases

A prospective study was carried out to evaluate the efficacy of serum neopterin and soluble IL-2 receptor (sIL-2R) concentrations in comparison to CD4 count to study the progression of HIV disease and monitor response to ART in HIV cases. One hundred newly diagnosed HIV seropositive subjects were recruited. CD4 counts were determined by FACS system. Serum neopterin and sIL-2R levels were measured using enzyme immunoassay. In our study, levels of neopterin and sIL-2R were significantly higher in subjects with CD4 <200 cells/μL (with S. neopterin levels of >25.1 nmol/L and sIL-2R levels of >47.1 pM as cutoff values for CD4 <200 cells/μL) compared to those in subjects with CD4 >200 cells/μL at baseline which indicate that these markers can be utilized for initiation of ART in HIV cases. The levels of these markers decreased significantly after initiation of ART. In patients with CD4 >200 cells/μL, these markers are helpful in predicting disease progression.

Reduction of splenic volume by steroid therapy in cases with autoimmune pancreatitis

Splenomegaly is sometimes recognized in autoimmune diseases and chronic pancreatitis; however, it has not yet been studied in autoimmune pancreatitis (AIP). The current study analyzed splenic volume and its associated factors in cases with AIP. Splenic volume was measured using computed tomography (CT) volumetric analysis in 46 cases with AIP and compared with 92 age- and gender-matched controls, and 46 disease controls (liver cirrhosis). Forty-six cases of chronic pancreatitis were also analyzed. Cases with AIP were investigated for factors associated with splenic volume and splenic volume change in response to steroid therapy. Splenic volume was significantly larger in AIP (149±86ml) than in controls (97±38ml) and in CP (108±79ml) (P<0.0001 and 0.0002), and was smaller than in disease controls (222±134ml) (P=0.003). In AIP cases, splenic volume was associated with age and gender (P=0.04 and 0.02), and splenomegaly was recognized in 20% (9/46) of cases. Abnormal uptake of (18)F-fluorodeoxyglucose was not detected in the spleen by positron emission tomography. Splenic vein (SpV) was frequently involved in AIP (67%), but was all recanalized after steroid therapy. Splenic volume in cases with AIP was minimized to 77% of the original (122±40ml) (P<0.0001) and this trend was remarkable in cases with splenomegaly (66%). In AIP, high serum IL-2 receptor level, diffuse pancreatic enlargement, and SpV stenosis were significantly associated with splenic shrinkage due to steroid treatment (P=0.002, 0.02, and 0.03). Splenomegaly was sometimes recognized in cases with AIP; however, these cases can be treated with steroids, especially in cases with diffuse pancreatic swelling and SpV stenosis.

Can serum interleukin-2 receptor alpha predict lymph node metastasis in early gastric cancer?

PurposeAlthough local resection like endoscopic mucosal resection for early gastric cancer is accepted as a treatment option, one of the most important drawbacks of such an approach is the inability to predictlymph node metastasis. The aim of this study was to evaluate the serum soluble receptor alpha for interleukin-2 (IL-2Rα) level as a predictor of lymph node metastasis in the patients with early gastric cancer.MethodsAssessment of pre-operative serum IL-2Rα levels was performed on 86 patients with early gastric cancer treated by gastrectomies combined with D2 lymph node resections and 20 healthy controls at Samsung Medical Center. Data on patient age and gender, tumor size, depth of invasion, histologic differentiation, and endoscopic findings were reviewed post-operatively. The submucosal lesions were divided into three layers (sm1, sm2, and sm3) in accordance with the depth of invasion.ResultsLymph node metastasis was observed in 16 patients (18.6%). Statistically, the serum IL-2Rα level was an important predictive factor of lymph node metastasis in undifferentiated gastric cancer, and the cut-off point for the predictive value of serum IL-2Rα level was 200 U/mL.ConclusionThe serum IL-2Rα level might be a good predictor of lymph node metastasis in undifferentiated early gastric cancer.

G-CSF therapy and catheter-related Gram-positive sepsis increase serum IL-2 receptor α level and may falsely suggest a relapse in children with soft tissue sarcomas unless serum beta2-microglobulin, lactate dehydrogenase and C-reactive protein levels are determined concomitantly

Many components of oncologic treatment increase serum sIL-2Rα level, which may falsely suggest a relapse. We tried to establish whether granulocyte colony stimulating factor (G-CSF) and central vein catheter (CVC)-related sepsis increase serum sIL-2Rα level to values on relapse of childhood soft tissue sarcomas (STS) and how to distinguish real relapse from a “false” one. Serum sIL-2Rα, B2-M, LDH, CRP and ESR levels and rates of markers’ elevated values were determined prospectively in 18 STS children: pre-treatmently (ST1), in complete remission (CR; ST2), in CR during G-CSF therapy (ST3), in CR during CVC-related sepsis (ST4), on relapse (ST5) and after treatment (ST6) and once in 50 healthy pediatric controls. It appeared that pre-treatment serum sIL-2Rα, LDH, CRP and ESR but not B2-M declined significantly with remission (ST2) achievement. At ST5 sIL-2Rα, B2-M, LDH and CRP increased from ST2 to ST1 values. SIL-2Rα levels at ST3 and ST4 rose significantly in all patients from ST2 to ST1 and ST5 values. At ST3 also serum LDH and B2-M increased to values at ST1 and ST5 and exceeded significantly those at ST2 and ST4. At ST4 CRP but not B2-M and LDH, rose significantly in most patients to values at ST1 and ST5. Thus, serum sIL-2Rα monitoring in pediatric STS reflects well response to chemotherapy unless samples are collected during G-CSF therapy or CVC-related sepsis. Determination of serum B2-M, LDH and CRP together with sIL-2Rα may help to distinguish between “real” relapse and “false” sIL-2Rα increase due to G-CSF administration or CVC-related sepsis.

Polymorphism in the Interleukin-1 Receptor Antagonist Gene Is Associated with Serum Interleukin-1 Receptor Antagonist Concentrations and Postoperative Opioid Consumption

The interleukin-1 receptor antagonist (IL-1Ra) is the principal determinant of IL-1β bioactivity within the IL-1 gene cluster, regulating IL-1α and IL-1β release. This study was designed to determine whether polymorphisms of the IL-1Ra gene (IL1RN) produce clinically measurable differences in serum IL-1Ra concentrations and opioid consumption in the postoperative period. Opioid consumption and pain scores were evaluated in 96 patients undergoing a nephrectomy. DNA was extracted from all patients, and the genotypes of IL1RN were determined by polymerase chain reaction amplification of the variable number of tandem repeats of 86 base pairs in intron 2 of IL1RN. The concentrations of serum IL-1Ra concentrations at baseline and at 24 h postoperatively in 58 subjects were measured. Differences in opioid consumption among the three genotype groups (IL1RN*1 homozygotes and *2 and *3 carriers) were statistically significant in the first and second 12-h postoperative periods (P = 0.010). The IL1RN*2 carrier group consumed 43% (95% CI, 38-48%) less opioids in the first 24 h after surgery than the IL1RN*1 homozygote group (P = 0.003). Differences in the serum IL-1Ra concentration among the three genotype groups were statistically significant at 24 h postoperatively (P = 0.003), with IL1RN*2 carriers having the highest serum IL-1Ra concentrations. The variable number of tandem repeats in intron 2 of IL1RN may contribute to interindividual variations in opioid consumption in the first 24 h after surgery. Patients homozygous for the IL1RN*1 allele have lower concentrations of IL-1Ra and require higher doses of opioids postoperatively than patients carrying at least one IL1RN*2 allele.

Endogenous Secretory Receptor for Advanced Glycation End Products Is Associated With Low Serum Interleukin-1 Receptor Antagonist and Elevated IL-6 in Older Community-Dwelling Adults

Advanced glycation end products (AGEs) are thought to cause inflammation through interaction with the receptor for AGEs (RAGE), therefore contributing to adverse aging-related processes. The relationship between AGEs, RAGE, and inflammation has not been well characterized. We examined the relationship of plasma endogenous secretory RAGE (esRAGE); carboxymethyl-lysine (CML), a circulating AGE; and inflammatory mediators in 1,298 adults, 20-97 years, who participated in the InCHIANTI study in Tuscany, Italy. Blood levels of esRAGE, CML, interleukin-1 receptor antagonist (IL-1RA), IL-1β, tumor necrosis factor-α (TNF-α), IL-6, IL-6 receptor (IL-6R), IL-18, C-reactive protein (CRP), transforming growth factor-β (TGF-β), and fibrinogen were measured. Log plasma esRAGE was associated with log IL-1RA (β = -0.069, SE = 0.036, p = .05) and log IL-6 (β = 0.077, SE = 0.035, p = .03), respectively, in separate multivariable linear regression models, adjusting for potential confounders. Log plasma esRAGE was also negatively associated with log TGF-β but did not reach statistical significance (β = -0.091, SE = 0.053, p = .09). Log plasma esRAGE was not significantly associated with log IL-1β, log TNF-α, IL-6R, log IL-18, or CRP. Log plasma CML was not associated with any of the inflammatory mediators except for IL-6R (β = -14.10, SE = 5.94, p = .02) and fibrinogen (β = 13.95, SE = 7.21, p = .05) in separate multivariable models, adjusting for potential confounders. Plasma esRAGE is correlated with higher IL-6 and lower IL-1RA. These findings suggest that plasma esRAGE plays a role in modulating inflammation, although the exact mechanisms remain to be elucidated.

Phase II Study of Sequential Therapy with Cladribine Followed by an Extended Course Rituximab in Patients with Hairy Cell Leukemia

AbstractAbstract 2458 Background:Although the nucleoside analogs cladribine (2CDA) and pentostatin are effective in the initial therapy of patients (pts) with HCL, complete remissions (CR) are not universal and relapses do occur. Methods:We have investigated whether an extended 8 week course of therapy with weekly rituximab after 2CDA can improve responses and eradicate minimal residual disease (MRD). Multicolor flow cytometry (MFC) was used to identify MRD by co-expression of CD103 and CD25 on CD19+ B-cells, with an assay sensitivity of 0.02%. MRD was also assessed by immunoglobulin heavy chain (IgH) polymerase chain reaction (PCR) assay using framework-1, -2 and -3 primer sets. 2CDA 5.6 mg/m2 IV was administered over 2 hours daily for 5 days. Approximately 1 month after initiation of 2CDA, bone marrow (BM) MRD was assessed and rituximab 375 mg/m2 IV was given weekly for 8 weeks. Responses were recorded and BM MRD was reevaluated after the completion of rituximab. Patients with untreated HCL (including variant form, HCLv) and those relapsing after 1 prior therapy were eligible. Results:To date, 45 pts have been treated including 38 with newly diagnosed HCL (4 with HCLv), and 7 (1 with HCLv) after relapse from 1 prior therapy (2CDA in 6 pts, chlorambucil in 1 pt). The median age of the pts was 54 years (range 32–89). Twenty five of 29 (86%) evaluable pts had mutated IgVH gene whereas IgVH was unmutated in 4 pts. 45 of 45 pts (100%) have achieved CR, defined as presence of no hairy cells in BM and blood with normalization of counts (ANC >1.5 × 109/L, Hgb >12.0 g/dL, Plt > 100 × 109/L), as well as resolution of splenomegaly, after completion of all therapy; MRD by MFC was positive in 33 of 37 (89%) evaluable pts after 2CDA therapy but became negative in 28 of 37 (76%) evaluable pts after rituximab. MRD by PCR was positive in 21 of 34 (62%) evaluable pts after 2CDA therapy and became negative in 27 of 38 (71%) evaluable pts after rituximab. Median serum IL-2 receptor level (reference range, 200–1100 U/mL) prior to initiation of therapy was 6661 U/mL (range, 458–44671). This fell to 1867 U/mL (range, 38–6661) after 2CDA and to 553 U/mL (range, 237–1673) after rituximab. The regimen was well tolerated with no grade 3 or 4 non-hematological adverse events directly related to the drugs. Only one pt (with HCLv) has relapsed; median CR duration has not been reached (range 3+ - 66+ months). Two pts developed another malignancy, pancreatic cancer in one and lung cancer in another, and died; while the pt with HCLv died from relapsed disease. Median survival duration has not been reached (range, 5+ - 71+ months). Conclusions:Chemo-immunotherapy with 2CDA followed by an extended course of rituximab may increase CR rate and duration and is effective in eradicating MRD in HCL. This regimen is also effective in pts with HCLv although responses may be less durable. Disclosures:Ravandi: Genentech: Research Funding. Off Label Use: Off label use of rituximab in hairy cell leukemia. Thomas: Novartis: Honoraria; Bristol-Meyer-Squibb: Honoraria; Pfizer:; Amgen: Research Funding.

Progressive external ophthalmoplegia as initial manifestation of sporadic late-onset nemaline myopathy

Sporadic late-onset nemaline myopathy (SLONM) is a rare disease and typically presents in patients older than 40 years with slowly progressive weakness in a limb-girdle distribution and unremarkable family history [1, 2]. Serum creatine kinase is usually normal, and electromyography may show myopathic changes. Nemaline rods in affected muscle fibers are considered the histopathological hallmark of nemaline myopathy and are mainly found within the sarcoplasm, inside of myonuclei, or both [3]. Ocular involvement has never been described in a patient with SLONM. We report a patient with SLONM suffering from prominent involvement of external ocular muscles. A 60-year-old female patient was reexamined for a chronic progressive oculopharyngeal syndrome that was present for 6 years. Initial symptoms were double vision and ptosis, followed by weakness of eye-closure. Two years after the onset of symptoms, she presented an exclusive picture of external ophthalmoplegia. During the following years she was unable to open or close her eyes voluntarily, lost her ability to whistle or smile, developed a hoarse voice and swallowing difficulties. There was no diurnal variation of symptoms, or fatigability. Family history for neuromuscular diseases was unremarkable. On examination she had complete bilateral ptosis and palsy of extraocular muscles, while pupillar size and pupillar reactions to light and accommodation were normal. She had a myopathic face with atrophy of masseter and temporalis muscles, severe bilateral facial palsy, and severe dysphonia. Strength was MRC grade 4 for neck flexion, head rotation, and neck extension. Further neurological examination was normal, notably fundoscopy and proximal and distal limb strength. Laboratory examinations provided normal values for standard parameters, serum creatine kinase, a comprehensive panel of autoimmune antibodies, including antibodies against acetylcholine receptor or muscle-specific kinase, anti-HIV 1/2 antibodies, and p24 antigen. Serum ACE, soluble Interleukin-2 receptor levels, serum and urine calcium levels, and repeated imaging studies ruled out sarcoidosis. Protein electrophoresis and immunofixation did not show any paraprotein, findings that rule out an association with HIV, sarcoidosis, or monoclonal gammopathy, as described in some patients in the literature [4–7]. MRI revealed symmetric atrophy of ocular muscles and fatty degeneration of pterygoideus medialis and masseter muscles, no signs of edema or contrast enhancement. Thorough neuromuscular transmission studies as well as spinal cord and brain imaging were unremarkable. No other organs were involved. Muscle biopsy of the sternocleidomastoideus revealed numerous rods, which appeared to be O. Wengert A. Meisel Department of Neurology, Charite-Universitatsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany

Increased level of serum interleukin-1 receptor antagonist subsequent to resolution of clinical symptoms in patients with West syndrome

The aim of this study was to evaluate whether proconvulsive interleukin-1β (IL-1β) and anticonvulsive IL-1 receptor antagonist (IL-1Ra) are markers of the effectiveness of treatment in patients with West syndrome (WS). We analyzed serum and cerebrospinal fluid (CSF) levels of IL-1β and IL-1Ra in 13 patients with WS. The serum IL-1Ra levels postimprovement (average, 384.6 pg/ml) in clinical and electroencephalographic (EEG) findings were significantly higher than the preimprovement values (average, 240.6 pg/ml). No significant difference in the preimprovement serum IL-1Ra levels was noted between the anticonvulsant (AED)-response and adrenocorticotropic hormone (ACTH)-response groups (260.0 pg/ml, n = 7 vs. 218.0 pg/m, n = 6) and the cryptogenic and symptomatic groups (290.1 pg/ml, n = 4 vs. 218.3 pg/m, n = 9), respectively; as for the preimprovement CSF levels, the AED-response group (114.5 pg/m; n = 3) and ACTH-response groups (138.0 pg/m; n = 6) and the cryptogenic (59.3 pg/m; n = 3) and symptomatic groups (165.6 pg/m; n = 6), respectively. Serum and CSF IL-1β levels were detected only in 3 patients preimprovement. Serum IL-1Ra levels were elevated subsequent to resolution of clinical and EEG findings in WS patients. A larger study should be conducted to clarify whether an immunological processes are concerned with the pathophysiology of WS.

Accelerated Increase in Serum Interleukin-1 Receptor Antagonist Starts 6 Years Before Diagnosis of Type 2 Diabetes

OBJECTIVEAlthough interleukin-1 receptor antagonist (IL-1Ra) treatment is associated with improved β-cell function and glycemic control in patients with type 2 diabetes, its role in the development of type 2 diabetes remains unclear. We used repeated measurements to characterize IL-1Ra trajectories in individuals who developed type 2 diabetes.RESEARCH DESIGN AND METHODSThis case-cohort study, nested within the Whitehall II cohort, was based on 335 incident type 2 diabetes cases and 2,475 noncases. We measured serum IL-1Ra levels at up to three time points per individual and estimated retrospective trajectories of IL-1Ra before diabetes diagnosis (case subjects) or end of follow-up (control subjects) using multilevel analysis. Models were adjusted for age, sex, and ethnicity.RESULTSIL-1Ra levels were already higher in the case than control subjects 13 years before diabetes diagnosis/end of follow-up (mean [95% CI] 302 [290–314] vs. 244 [238–249] pg/ml). In control subjects, IL-1Ra levels showed a modest linear increase throughout the study period. In case subjects, IL-1Ra trajectories were parallel to those in control subjects until 6 years (95% CI 7.5–4.5) before diagnosis and then rose steeply to 399 (379–420) pg/ml at the time of diagnosis (P < 0.0001 for slope difference). Adjustment for BMI and waist circumference as time-varying covariates had little impact on these trajectories.CONCLUSIONSWe show elevated IL-1Ra levels for 13 years and an accelerated increase during the last 6 years before type 2 diabetes diagnosis, indicating the presence of an anti-inflammatory response that may act to counterbalance the metabolic and immunologic disturbances that precede type 2 diabetes.

A study on interleukin 2 and soluble interleukin 2 receptor in serum and bronchoalveolar lavage fluid from patients with farmer's lung

Interleukin 2 (IL-2) and soluble Interleukin 2 receptor (IL-2R) were assayed in serum and bronchoalveolar lavage fluid (BALF) from patients with farmer's lung. Patients with farmer's lung had significantly higher levels of soluble IL-2R in serum and BALF than normal controls. The level of soluble IL-2R was correlated with the disease activity, and fell to within the normal range after successful treatment with corticosteroids. On the other hand, asymptomatic dairy farmers with precipitating antibodies against Micropolyspora faeni antigen or Thermoactinomyces vulgaris antigen had the same levels of soluble IL-2R in their serum and BALF as normal controls. IL-2 levels in serum and BALF were significantly higher in patients with farmer's lung than in normal controls; however, asymptomatic patients had low levels comparable to those of normal controls. These results indicate that soluble IL-2R could be a sensitive parameter for evaluation of the activity of this disease. It is also suggested that the IL-2/IL-2R system is important in the pathogenesis of hypersensitivity pneumonitis.

F-18 FDG PET/CT Findings in A Case of Multifocal Nodular Lymphoid Hyperplasia of the Lung

Pulmonary nodular lymphoid hyperplasia is a rare benign disease with polyclonal lymphoid proliferation. We describe a 67-year-old man with atypical manifestation of this disease with bilateral multifocal lesions including subcentimeter nodules and infiltrate, which showed only faint F-18 FDG uptake on PET/CT scan and spontaneous regression. Before obtaining histopathologic confirmation, the differential diagnosis of the multifocal lesions included metastases or malignant lymphoma, because of the history of extrathoracic malignancy, elevated serum interleukin-2 receptor, and temporal growing of the lesions. Histopathologic confirmation appears indispensable for the definitive diagnosis of pulmonary nodular lymphoid hyperplasia, as multifocal small lesions of malignancy, including mucosa-associated lymphoid tissue lymphoma and benign diseases such as plasmacytoma and inflammatory pseudotumor can also show only faint FDG uptake, with overlapping clinical and radiologic features.

Clinical utility of serum Interleukin-1 receptor antagonist levels as a diagnostic and prognostic assay in surgical patients

Clinical utility of serum Interleukin-1 receptor antagonist levels as a diagnostic and prognostic assay in surgical patients

Low‐dose and short‐term cyclosporine treatment in patients with chronic idiopathic urticaria: A clinical and immunological evaluation

The present study aimed to evaluate the effectiveness of 2.5 mg/kg/day cyclosporin (CsA) treatment in patients with severe chronic idiopathic urticaria (CIU) and the impact of CsA treatment on several cytokines involved in the etiopathogenesis of CIU. Twenty-seven CIU patients and 24 healthy control subjects were included in the study. The autologous serum skin test (ASST) for autoantibodies and urticaria activity scoring (UAS) were measured for the evaluation of the clinical severity and the response to therapy, and the serum levels of interleukin (IL)-6, IL-8, IL-2 receptor, IL-1beta, tumor necrosis factor (TNF)-alpha and IL-5 were measured. The mean UAS score was 32.07 +/- 7.05 and 6.22 +/- 3.84 before and after CsA treatment, respectively. The serum IL-2 receptor, TNF-alpha and IL-5 levels of patients before CsA treatment were statistically higher than those of the control group (P = 0.001), and after 4 weeks of CsA therapy the mean IL-2R, TNF-alpha and IL-5 levels were significantly decreased. The data from this study demonstrate that CsA therapy is efficient and safe for CIU patients. Increase in clinical efficacy and marked decreases in serum cytokine levels suggest that inhibition of cytokine generation is involved in the action of the drug in this clinical setting.

Is the Determination of the Soluble Interleukin-2 Receptor after Application of Interleukin-2 Receptor Antibodies Still Appropriate for Immunological Monitoring after Renal Transplantation?

Introduction: The use of monoclonal antibodies against the α-chain of the membrane-bound interleukin-2 receptor (IL-2Rα) as immune suppressants causes characteristic changes in the levels of soluble interleukin-2 receptor (sIL-2R) in serum and urine. Methods: 38 kidney transplant patients were included in this study. 28 of them received an induction therapy with the IL-2R antibody basiliximax (Simulect®) in addition to standard immunosuppression, 10 patients constituted the control group. Results: Time courses of sIL-2R levels of Simulect patients with and without complications after transplantation have been compared. It turned out that of a total of 18 cases with complications 15 cases could be identified by their elevated sIL-2R levels, which corresponds to a sensitivity of 83%. Conclusion: Acute rejection, CMV infection, extrarenal bacterial infection and pyelonephritis in the transplant all cause a significant increase of the sIL-2R level even after application of Simulect.