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At least 19 recordsLinked to original sources

Serum soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha levels in children with celiac disease: response to treatment.

OBJECTIVES: T-cell mediated immune response to dietary gluten and cytokines release are important for the enteropathy seen in celiac disease. We investigated the serum levels of soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha in celiac children before and after gluten exclusion. METHODS: Cytokine levels were determined using enzyme immunoassay in serum from 12 untreated celiac patients, 16 treated celiac patients on a gluten-free diet for at least two years, and from 26 control children. Eight of 12 untreated patients were also investigated at 6 and 12 months after gluten exclusion. Serum IgA antiendomysium antibodies were also assayed by indirect immunofluorescence. RESULTS: Soluble interleukin-2 receptor and interleukin-6 levels were significantly increased in untreated celiac patients compared with treated and control children. There was no difference in the tumor necrosis factor-alpha levels between the groups. Soluble interleukin-2 receptor levels were the only ones significantly decreased at 12 months after gluten exclusion. However, soluble interleukin-2 receptor and interleukin-6 levels at 12 months were significantly higher compared with controls. Antiendomysium antibodies had a diagnostic sensitivity of 100% and the titers decreased significantly after 12 months of gluten exclusion. A significant positive correlation was found between antiendomysium antibody titers with both soluble interleukin-2 receptor and interleukin-6 values. CONCLUSIONS: The serum soluble interleukin-2 receptor and interleukin-6 levels may be used as a noninvasive measure of celiac disease activity and response to treatment.

Adolescent↗

Identification of the second subunit of the murine interleukin-5 receptor: interleukin-3 receptor-like protein, AIC2B is a component of the high affinity interleukin-5 receptor.

Murine interleukin-5 (IL-5) binds to its receptor with high and low affinity. It has been shown that the high affinity IL-5 receptor (IL-5-R) is composed of at least two membrane protein subunits and is responsible for IL-5-mediated signal transduction. One subunit of the high affinity IL-5-R is a 60 kDa membrane protein (p60 IL-5-R) whose cDNA was isolated using the anti-IL-5-R monoclonal antibody (mAb), H7. This subunit alone binds IL-5 with low affinity. The second subunit does not bind IL-5 by itself, and is expressed not only on IL-5-dependent cell lines but also on an IL-3-dependent cell line, FDC-P1. Expression of the p60 IL-5-R cDNA in FDC-P1 cells, which do not bind IL-5, reconstituted the high affinity IL-5-R. We have characterized the second subunit of the IL-5-R by using another anti-IL-5-R mAb, R52.120, and the anti-IL-3-R mAb, anti-Aic-2. The anti-Aic-2 mAb down-regulated binding of IL-5 to an IL-5-dependent cell line, Y16. Both R52.120 and anti-Aic-2 mAbs recognized membrane proteins of 130-140 kDa expressed on FDC-P1 and Y16 cells. The R52.120 mAb recognized both murine IL-3-R (AIC2A) and its homologue (AIC2B) expressed on L cells transfected with suitable cDNAs. The high affinity IL-5-R was reconstituted on an L cell transfectant co-expressing AIC2B and p60 IL-5-R, whereas only the low affinity IL-5-R was detected on a transfectant co-expressing AIC2A and p60 IL-5-R.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Type I IgE receptor, interleukin 4 receptor and interleukin 13 polymorphisms in children with nephrotic syndrome.

Polymorphisms in the genes encoding the high-affinity IgE receptor, the interleukin 4 (IL4) receptor and IL13 can be associated with the development of asthma and allergy. Although several studies have described an association between atopy and idiopathic childhood nephrotic syndrome (NS), it is not clear whether this association is of a causal nature. Furthermore, it is not known whether these polymorphisms are associated with the clinical course of NS. A total of 84 children (52 male and 32 female; mean age 12.1 years) with NS were included in the present study. Of these, 78 could be classified as either atopic or non-atopic. Atopy was defined by elevated IgE levels (>100 k-units/l) and/or a positive history of atopy (33 of 78 patients). DNA was extracted from blood collected in EDTA tubes, and polymorphisms at positions 50 and 551 of the IL4 receptor, position 110 of IL13 and position 181 of the high-affinity IgE receptor were investigated by sequence-specific PCR or direct sequencing. Although we noted a strong tendency towards a higher allele frequency of polymorphisms in children with atopy and NS compared with children with NS but without atopy (IL4 50, 30% compared with 18%; IL4 551, 39% compared with 31%; IL13 110, 45% compared with 33%; IgE 181, 12% compared with 13%), these differences did not reach statistical significance. There were no differences in the frequency of polymorphisms between the different clinical courses of NS (frequent relapsers, steroid-dependent or steroid-resistant NS). We conclude that polymorphisms in the IL4 receptor, the high-affinity IgE receptor and IL13 do not seem to predict the clinical course of NS, despite the fact that serum IgE elevations are more frequent in patients with NS than in normal control subjects. The investigated polymorphisms may contribute to the IgE switch in patients with NS.

Adolescent↗

SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling.

The Toll-like receptor-interleukin 1 receptor signaling (TLR-IL-1R) receptor superfamily is important in differentially recognizing pathogen products and eliciting appropriate immune responses. These receptors alter gene expression, mainly through the activation of nuclear factor-kappaB and activating protein 1. SIGIRR (single immunoglobulin IL-1R-related molecule), a member of this family that does not activate these factors, instead negatively modulates immune responses. Inflammation is enhanced in SIGIRR-deficient mice, as shown by their enhanced chemokine induction after IL-1 injection and reduced threshold for lethal endotoxin challenge. Cells from SIGIRR-deficient mice showed enhanced activation in response to either IL-1 or certain Toll ligands. Finally, biochemical analysis indicated that SIGIRR binds to the TLR-IL-1R signaling components in a ligand-dependent way. Our data show that SIGIRR functions as a biologically important modulator of TLR-IL-1R signaling.

Animals↗

Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is critical for mediating Toll-like receptor (TLR)-interleukin 1 receptor (IL-1R) signaling and subsequent activation of NF-kappaB and AP-1, transcriptional activators of innate immunity. Here we show that beta-arrestins, a family of multifunctional proteins, directly interacted with TRAF6 after TLR-IL-1R activation. Formation of the beta-arrestin-TRAF6 complex prevented autoubiquitination of TRAF6 and activation of NF-kappaB and AP-1. Endotoxin-treated beta-arrestin 2-deficient mice had higher expression of proinflammatory cytokines and were more susceptible to endotoxic shock. Thus, beta-arrestins are essential negative regulators of innate immune activation via TLR-IL-1R signaling.

Animals↗

Soluble interleukin-2 receptor, interleukin-2 and interleukin-4 in sera and supernatants from patients with progressive systemic sclerosis.

We studied the sera of patients with progressive systemic sclerosis (PSS) for elevated levels of soluble interleukin-2 receptor (sIL-2R), interleukin-2 (IL-2) and interleukin-4 (IL-4). We also measured IL-2, IL-4 and B cell growth factor (BCGF) activity in supernatants of peripheral blood mononuclear cells from the same patients. The finding of elevated serum sIL-2R and IL-2, and the increased levels of IL-2, IL-4 and BCGF activity in culture supernatants indicates that T lymphocyte hyperactivity likely play a major role in PSS. The failure to detect under our experimental conditions a direct proliferative effect of recombinant IL-2 on enriched normal B cells might suggest that IL-4 is the cytokine mainly responsible of the BCGF activity recovered in PSS supernatants.

Adult↗

Elevated serum levels of soluble interleukin 2 receptor, interleukin 2 and neopterin in diffuse and limited scleroderma: effects of chlorambucil.

In a study of 48 patients with systemic sclerosis (SSc). elevated serum levels of soluble interleukin 2 receptor (IL-2R), interleukin 2 (IL-2) and neopterin (indicators of lymphocyte/monocyte activation) were noted in 100, 44 and 40% of early untreated patients with SSc (11 diffuse, 5 Limited). Levels of IL-2R, but not IL-2 or neopterin, were lower in patients with longer duration of disease and possibly with chlorambucil therapy. Pharmacologic alterations of markers of humoral or cell mediated immunity may not be an accurate reflection of clinical efficacy of chlorambucil.

Adult↗

Ten-year follow-up study of allergen-specific immunoglobulin E and immunoglobulin G4, soluble interleukin-2 receptor, interleukin-4, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in serum of patients on immunotherapy for perennial allergic rhinitis.

Recent double-blind placebo-controlled trials for perennial allergic rhinitis have all clearly shown the efficacy of immunotherapy. Although several mechanisms for the clinical efficacy of immunotherapy have been proposed, the exact mechanisms related to the clinical effect still remain unclear. Since immunotherapy is a form of systemic treatment and its clinical benefit is likely to be, at least in part, a consequence of its systemic effects on different phases of immunological events, our study focused exclusively on several immunological parameters in serum. A total of 47 patients with perennial allergic rhinitis due to Dermatophagoides farinae enrolled in this prospective study. Venous blood was collected for determination of specific immunoglobulin (Ig)E, specific IgG4, soluble interleukin-2 receptor (IL-2R), interleukin-4 (IL-4), soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1), six times from 20 untreated patients and 27 patients on immunotherapy, at enrolment, and 1, 2, 3, 5, and 10 years after enrollment. No specific IgE, IgG4, soluble IL-2R, IL-4 and soluble ICAM-1 levels changed significantly for a span of 10 years in the untreated patients. By contrast, immunotherapy affected serum levels of specific IgE, specific IgG4, soluble IL-2R, IL-4 and soluble ICAM-1, but not of soluble VCAM-1. The rates of increase in specific IgG4 and the rates of decrease in soluble IL-2R were correlated with the rates of decrease in symptom scores during the first 3 years, but not 5 and 10 years after the course of immunotherapy. On the other hand, the rates of decrease in specific IgE, IL-4 and soluble ICAM-1 were significantly correlated with the rates of decrease in symptom scores at 5 and 10 years, but not during the first 3 years. Each immunological modulation by immunotherapy was likely to be involved in the working mechanism related to clinical efficacy at different phases of immunotherapy.

Adolescent↗

Aggressive non-Hodgkin's lymphoma: concomitant evaluation of interleukin-2, soluble interleukin-2 receptor, interleukin-4, interleukin-6, interleukin-10 and correlation with outcome.

The purpose of this study was to assess the prognostic value of a large panel of cytokines in aggressive non-Hodgkin's lymphoma (NHL) and to confront it to parameters of the International Prognostic Index (IPI). It investigated the concomitant determination of interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-10 (IL-10) on a uniform population of 116 previously untreated patients. Commercially available enzyme-linked immunoassay kits were used for cytokines measurements. Results were correlated with complete remission (CR), overall survival (OS) and failure free survival (FFS). In univariate analysis, sIL-2R and IL-6 demonstrated prognostic significance for CR (p = 0.016 and p = 0.048), OS (p = 0.0011 and p = 0.0387) and FFS (p = 0.0001 and p = 0.0363), but multi-variate analysis failed to demonstrate an independent prognostic significance. In the intermediate group risk defined by IPI, patients presenting high level of sIL-2R or IL-6 demonstrated lower CR rate and survival than those with low level. In conclusion, sIL-2R and IL-6 serum levels are elevated in high grade NHL and are correlated to CR, OS and FFS, but this study did not support their independent prognostic value. However, sIL-2R and IL-6 measurements may improve risk assignment by IPI and allow a better prognostic evaluation of patients with intermediate prognosis NHL.

Adult↗

Effects of interferon-alpha2a treatment on serum levels of tumor necrosis factor-alpha, tumor necrosis factor-alpha2 receptor, interleukin-2, interleukin-2 receptor, and E-selectin in Behçet's disease.

This study was performed to investigate serum levels of various cytokines and E-selectin in patients with Behçet's disease (BD) before and after treatment with interferon-alpha2a (IFN-alpha). The study population consisted of 22 patients with active BD; 15 age- and sex-matched healthy adults served as the control group. IFN-alpha (3 million units subcutaneously) was given to all patients twice a week for 3 months. Twenty of twenty-two patients experienced clinical improvement with this therapy. Pre- and post-treatment serum levels of tumor necrosis factor-alpha (TNF-alpha), TNF-alpha2-receptor (TNFalpha2R), interleukin-2 (IL-2), IL-2 receptor (IL-2R), and E-selectin were measured by sandwich-type enzyme immunoassay. Baseline E-selectin, TNF-alpha, and TNF-alpha2R levels of the patients were increased in comparison with the control group and post-treatment values. However, IL-2 and IL-2R levels did not change either with treatment or compared with the control group levels. In conclusion, these results confirm the previously described efficacy of IFN-alpha in the treatment of BD. Serum levels of TNF-alpha, TNF-alpha2R, and E-selectin are prominently increased during active stage of the disease, indicating presence of immune system activation and endothelial injury/activation. Improvement of the pathological cytokinemia and endothelial disturbance accompany interferon-alpha-induced disease remission.

Adult↗

Microinvasive Nd:YAG laser therapy of early glottic carcinoma and its effect on soluble interleukin-2 receptor, interleukin-2, and natural killer cells.

OBJECTIVE: To investigate the effectiveness of microinvasive Nd:YAG laser therapy in human glottic Tis and T1 carcinomas, as well as its effect on the cellular immune function of the tumor-bearing hosts. STUDY DESIGN: We treated 34 patients with microinvasive Nd:YAG laser therapy and evaluated its effect on the cellular immune function of the host. METHODS: Thirty-four patients with glottic Tis or T1 squamous cell carcinoma were treated with fiberoptic laryngoscopic Nd:YAG laser surgery. Both before and after therapy, serum levels of soluble interleukin-2 receptor (SIL-2R) and interleukin-2 (IL-2), as well as natural killer (NK) cell activity, were determined by means of double-antibody sandwich technique, tritiated thymidine-deoxyribonucleoside incorporation, and iodine 125-uridine-deoxyribonucleoside release technique, respectively. RESULTS: All 34 patients tolerated the procedure well. A 3- to 7-year follow-up in a subgroup of 27 patients resulted in an estimated cure rate of 85.2% (23 of 27 patients). In all 27 patients with a regular follow-up, a subjective improvement of phonation was noted after therapy to various degrees. In 74% (20 of 27 patients), voice and speech subjectively recovered to almost normal levels. The post-therapy serum levels of SIL-2R were significantly declined (P <.001), whereas those of IL-2 and the NK activity were significantly elevated (P <.001) as compared with those detected before therapy. CONCLUSIONS: Therapy with fiberoptic laryngoscopic Nd:YAG laser surgery is simple, safe, effective and only minimally invasive for patients with glottic Tis or T1 carcinoma. At the same time, it has an immunoenhancing effect on its host.

Adult↗

Circulating soluble tumor necrosis factor receptors, interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-6 levels in rheumatoid arthritis. Longitudinal evaluation during methotrexate and azathioprine therapy.

OBJECTIVE: To assess whether circulating concentrations of soluble tumor necrosis factor receptors (sTNFR; p55 and p75), soluble interleukin-2 receptors (sIL-2R), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) reflect clinical response and whether changes are dependent on the drug used in rheumatoid arthritis (RA) patients taking methotrexate (MTX) or azathioprine (AZA). METHODS: These cytokines and soluble receptors were assessed in 20 control subjects and serially for up to 48 weeks in 61 RA patients, by bioassay (IL-6) and immunoassays (sTNFR, sIL-2R, TNF alpha, and IL-6). RESULTS: Concentrations of p55 and p75, sIL-2R, and TNF alpha (but not IL-6) were significantly higher in RA patients than in controls. Significant decreases in sIL-2R and p55 concentrations were associated with clinical improvement and were observed in patients treated with MTX, but not AZA. Both treatments induced decreases in IL-6 concentrations, but circulating AZA (or its metabolites) appears to interfere with the measurement of IL-6 bioactivity. TNF alpha and p75 levels did not show significant changes. CONCLUSION: Measurement of circulating sIL-2R, p55, and IL-6 may be useful in the evaluation of RA disease activity and response to therapy. Interference by circulating levels of drugs must be ruled out when bioassays are used to evaluate cytokine levels.

Arthritis, Rheumatoid↗

Influence of corticosteroid pulse therapy on the serum levels of soluble interleukin 2 receptor, interleukin 6 and interleukin 8 in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the influence of corticosteroid pulse (CP) therapy on soluble interleukin 2 receptor (sIL-2R), interleukin 6 (IL-6) and IL-8 levels in patients with active rheumatoid arthritis (RA). METHODS: Twenty-five patients with active RA were studied before and after treatment with intravenous CP therapy. In 12 patients lymphocyte subsets were also assessed. RESULTS: All patients showed a significant decrease in clinical disease activity variables after 4 to 8 weeks of CP therapy. Baseline levels of sIL-2R were higher among patients with active RA than healthy controls; after CP therapy, sIL-2R levels decreased significantly, but not as much as the erythrocyte sedimentation rate or C-reactive protein. In most cases baseline levels of both IL-6 (n = 23) and IL-8 (n = 17) could be measured and both decreased significantly after CP therapy. Cortisol levels were suppressed shortly after CP therapy but had returned to pretreatment values at 4 weeks. After CP therapy there was a temporary increase in the number of HLA-DR positive cells and a decrease in the number of CD3 positive cells, while the CD4/CD8 ratio and IL-2 receptor (CD25) positive cells remained unchanged. CONCLUSION: High dose corticosteroids influence serum levels of sIL-2R, IL-6 and IL-8 in patients with active RA.

Adult↗

Soluble serum interleukin-2 receptor, interleukin-6 and interleukin-1a in patients with endometriosis and in controls.

The aim of this study was to verify to what extent danazol alters cell-mediated immunity. To this end, cell-mediated immunity was studied in 10 infertile patients with endometriosis and in 10 normal controls. Nonspecific parameters studied included serum SIL-2R, IL-6 and IL-1a levels. We also investigated the effect of treatment with Danazol on the levels of SIL-2R, IL-6 and IL-1a in women with endometriosis. Blood SIL-2R, IL-6 and IL-1a levels were measured in endometriotic women before treatment, during the last fifteen days of a 6-months course of Danazol and three months after treatment. Only one blood sample was taken from 10 women without endometriosis. SIL-2R, IL-6 and IL-1a levels were higher in women with endometriosis before treatment compared with controls. Administration of the drug significantly reduced the levels of SIL-2R (P < 0.001), IL-6 (P < 0.05) and IL-1a (P < 0.01). Our findings suggest that endometriosis is a condition which induces a rise in interleukin levels. Danazol also appears significantly to reduce endometriosis-associated autoimmune abnormalities.

Adult↗

Multilocus interactions at maternal tumor necrosis factor-alpha, tumor necrosis factor receptors, interleukin-6 and interleukin-6 receptor genes predict spontaneous preterm labor in European-American women.

OBJECTIVE: We hypothesize that genetic variations (single nucleotide polymorphisms-SNPs) in the tumor necrosis factor-alpha (TNF-alpha), TNF receptors (TNFRI and TNFRII), interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes predict high-risk status for spontaneous preterm birth (sPTB) in European-American women. In this study we examine the allelic and genotypic variations and the gene-gene interactions in the TNF-alpha, TNFRs, IL-6, and IL-6R genes in maternal DNA samples by using a case-control model. STUDY DESIGN: Maternal DNA from cases of sPTB after preterm labor (n = 101) and controls (normal term labor and delivery) (n = 321) were genotyped for SNPs in the TNF-alpha (6), TNFRI (6), TNFRII (7), IL-6 (5), and IL-6R (3) loci. SNPs were tested for both allele and genotype differences (cases vs controls) with the use of standard genetic epidemiologic methods. Multilocus interaction was assessed with multifactor dimensionality reduction analysis (MDR) to test all single and multilocus combinations for the ability to predict sPTB. RESULTS: Few significant allelic and genotypic associations were detected between cases and controls in maternal DNA. Single locus analysis documented independent association of SNPs at -7294 (allele and genotype) of TNFRI and 24660 (genotype) TNFRII loci with sPTB. MDR revealed a significant 3 locus model that includes SNPs -3448 of TNF-alpha, -7227 of IL-6, and 33314 of IL-6R. This interactive model allowed the successful prediction of pre- to low-risk genotypes is 3.50 (95% CI 2.52-4.87, P < .001). CONCLUSION: This is the first report to document a multilocus interaction in sPTB that predicts 65.2% of the cases in a European-American sample. Although putatively significant associations with sPTB were seen at a few single locus sites in TNFRI and TNFRII, they were not as predictive as the 3-locus model produced by MDR, suggesting the use of multilocus analyses in gene association studies of complex disease such as sPTB.

Adult↗

[Differential diagnostic and prognostic value of serum cytokines (soluble CD30, soluble interleukin-2 receptor, interleukin-10 and interleukin-6) in Hodgkin's disease and lymphosarcomas].

AIM: Determination of the importance of serum cytokines (sCD30, sIL-2R, IL-10, IL-6) for diagnosis, response to chemotherapy and remission in patients with lymphogranulomatosis and lymphosarcoma. MATERIAL AND METHODS: Cytokine concentrations were measured in 87 samples of serum (plasma) from 54 patients by ELISA. Diagnosis of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) was made histologically in 24 and 30 patients, respectively. RESULTS: The threshold concentrations of sCD30 (and less specific sIL-2R) for HD and NHL patients allowed to estimate sensitivity to chemotherapy after the second course. The threshold concentration of IL-10 can distinguish HD from NHL. Changes in IL-6 concentrations were nonspecific. CONCLUSION: On the basis of the threshold concentrations of sCD30 and IL-10 we offer the scheme of lymphoma diagnosis and prediction of the disease sensitivity to chemotherapy which reduce the duration of lymphoma restaging.

Adolescent↗

Stability of interleukin 6, soluble interleukin 6 receptor, interleukin 10 and CC16 in human serum.

The stability of interleukin 6 (IL-6), its soluble receptor (sIL-6R), IL-10 and CC16 or uteroglobin (an endogenous cytokine inhibitor) in human serum was examined using an accelerated stability testing protocol according to the Arrhenius equation. Further, the effect of time delay between blood sampling and sample processing, clotting temperature and repeated freeze-thaw cycles on serum levels of these proteins were determined. Paired serum samples were stored at 4 degrees C, 20 degrees C, 30 degrees C and 40 degrees C for 1 to 21 days. We found that IL-6 and CC16 concentrations did not change at 4 degrees C, 20 degrees C and 30 degrees C. Interleukin-6 concentrations significantly declined after 11 days at 40 degrees C. The concentrations of sIL-6R and IL-10 did not change at 4 degrees C but significantly decreased at 20 degrees C (after 21 and 14 days respectively), 30 degrees C and 40 degrees C (after 1 day at both temperatures for both cytokines). Arrhenius-plots indicated that sIL-6R and IL-10 are stable for at least several years at -20 degrees C and -70 degrees C, respectively. Since their relative stability, no Arrhenius-plot could be calculated for IL-6 and CC16. The concentrations of the proteins examined were not significantly altered by repeated freeze-thaw cycles, nor by extended clotting times at 4 degrees C or 20 degrees C. We conclude that serum samples for the determination of IL-6, sIL-6R and CC16 can be stored at -20 degrees C for several years, but for IL-10 determinations, storage at -70 degrees C is recommended.

Blood Coagulation↗

Soluble interleukin-6 receptor, interleukin-10 and granulocyte colony-stimulating factor in acute pyelonephritis: relationship to markers of bacterial virulence and renal function.

BACKGROUND: Cytokines and cytokine receptors are involved in the systemic and local inflammatory response in patients with urinary tract infections. METHODS: We examined urine and serum concentrations of soluble IL-6 receptor (sIL-6R), IL-10 and granulocyte colony-stimulating factor (G-CSF) in 29 women with acute pyelonephritis caused by Escherichia coli 2 weeks after the infection, during the subsequent episode of cystitis or asymptomatic bacteriuria and also later when the same patients were free from bacteriuria. Concentrations of sIL-6R, IL-10 and G-CSF were related to the expression of five virulence markers of E. coli and to glomerular filtration rate (GFR) after pyelonephritis. RESULTS: On admission because of acute pyelonephritis the serum concentration of sIL-6R was similar to that of 12 healthy controls. Two weeks after the infection when all patients had received antibiotic treatment, the serum concentration of sIL-6R was significantly higher compared to that on admission (p < 0.001) and also higher compared to healthy controls (p = 0.001). Patients with increased concentrations of sIL-6R in serum 2 weeks after infection had significantly lower GFR at follow-up (p < 0.05). Patients with acute pyelonephritis had higher concentrations of G-CSF and IL-10 in serum compared to healthy subjects (p < 0.001 and p = 0.06, respectively). G-CSF in serum was higher in patients infected by E. coli producing cytotoxic necrotizing factor (p < 0.05). Patients infected by strains producing hemolysin had lower concentrations of sIL-6R (p < 0.001). Patients with detectable levels of the anti-inflammatory cytokine IL-10 in serum had significantly higher concentrations of IL-6 and the soluble tumor necrosis factor receptors I and II in serum as compared to patients in whom IL-10 was not detectable (p < 0.001, p = 0.001 and p < 0.05, respectively. CONCLUSION: These investigations, together with our previous findings summarized in this paper, contribute to an increased understanding of the local and systemic inflammatory response arising in response to acute pyelonephritis.

Acute Disease↗