interleukin-8 and Hypereosinophilic-Syndrome

Churg-Strauss syndrome (CSS) and hypereosinophilic syndrome (HES) overlap considerably in clinical presentation. A reliable means of distinguishing between these groups of patients is needed, especially in the setting of glucocorticoid therapy.. A retrospective chart review of 276 adult subjects referred for evaluation of eosinophilia > 1500/μl was performed, and subjects with a documented secondary cause of eosinophilia or a PDGFR -positive myeloproliferative neoplasm were excluded. The remaining subjects were assessed for the presence of American College of Rheumatology (ACR) criteria. Laboratory and clinical parameters were compared between subjects with biopsy-proven vasculitis (CSS; n = 8), ≥4 ACR criteria (probable CSS; n = 21), HES with asthma and/or sinusitis without other CSS-defining criteria (HESwAS; n = 20), HES without asthma or sinusitis (HES; n = 18), and normal controls (n = 8). Serum biomarkers reported to be associated with CSS were measured using standard techniques.. There were no differences between the subjects with definite or probable CSS or HES with respect to age, gender, or maintenance steroid dose. Serum CCL17, IL-8, and eotaxin levels were significantly increased in eosinophilic subjects as compared to normal controls, but were similar between the eosinophilic groups. Serum CCL17 correlated with eosinophil count (P < 0.0001, r = 0.73), but not with prednisone dose.. In patients with a history of asthma and sinusitis, distinguishing between ANCA-negative CSS and PDGFR-negative HES is difficult because of significant overlap in clinical presentation and biomarker profiles.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chemokine CCL11; Chemokine CCL17; Churg-Strauss Syndrome; Female; Humans; Hypereosinophilic Syndrome; Interleukin-8; Male; Middle Aged; Retrospective Studies; Young Adult

Interleukin-18 (IL-18), a proinflammatory cytokine, leads to IFN-gamma production by NK or T cells, induces Th1 differentiation and suppresses IgE synthesis by B cells when acting on responding cells together with IL-12. IL-18 also exhibits biological activities related to allergic inflammation such as histamine or IL-4 release from basophils and accumulation of eosinophils in localized lesions in allergic model mice. In this study, Reverse transcription (RT)-PCR analysis revealed that IL-18 receptor alpha chain mRNA was expressed in both freshly prepared eosinophils and two eosinophilic cell lines (YY-1 and EoL-1 cells). Flow cytometry and RT-PCR analyses revealed that the treatment of YY-1 cells with n-butyric acid promoted cell maturation and caused an enhancement of IL-18 receptor alpha chain expression. IL-18 had little effect on the survival of peripheral eosinophils, but it dose-dependently augmented IL-8 synthesis by YY-1 cells. In addition, IL-18-mediated up-regulation of IL-8 expression in eosinophils from a patient suffering from hyper-eosinophilic syndrome was confirmed. Our findings using peripheral blood eosinophils and eosinophilic cell line suggest the functional importance of IL-18 in the induction of IL-8 and a potential proinflammatory role in allergy.

Topics: Butyric Acid; Cell Differentiation; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Eosinophils; Flow Cytometry; Gene Expression Regulation; Humans; Hypereosinophilic Syndrome; Interleukin-18; Interleukin-18 Receptor alpha Subunit; Interleukin-8; Receptors, Interleukin; Receptors, Interleukin-18; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

We evaluated the ability of eosinophil granule major basic protein (MBP) to stimulate interleukin (IL)-8 production by neutrophils. MBP over the concentration range of 0.1 to 10 microM stimulated the release of up to approximately 8 ng/ml IL-8. Incubation with 2 microM MBP showed that, after a 1 h lag, the level of IL-8 release increased with time for approximately 10 h. At the 2 microM concentration, eosinophil cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase did not stimulate significant levels of IL-8 production. MBP stimulated 2-fold increases in IL-8 messenger RNA (mRNA) after 1 and 3 h of incubation, which were blocked by pretreatment with actinomycin D. However, stimulation with MBP did not produce an increase in the binding activity of nuclear factor (NF)-kappaB or activator protein-1. No NF-IL-6 binding activity was detected in the same nuclear extracts. In addition, stimulation with MBP prolonged the stability of IL-8 mRNA. MBP also induced transient increases in mRNA for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, but did not stimulate the release of either chemokine. These findings indicate that MBP is selective among the eosinophil granule proteins as a stimulus for neutrophil IL-8 release and, further, that stimulation of neutrophil IL-8 release by MBP involves both transcriptional and posttranscriptional regulation. We postulate that MBP-induced release of IL-8 by neutrophils may contribute to the pathophysiology of acute asthma and other inflammatory lung diseases.

Topics: Blood Proteins; Chemokine CCL3; Chemokine CCL4; Dactinomycin; Dose-Response Relationship, Drug; Eosinophil Granule Proteins; Eosinophil-Derived Neurotoxin; Eosinophils; Humans; Hypereosinophilic Syndrome; Interleukin-6; Interleukin-8; Macrophage Inflammatory Proteins; Neutrophils; NF-kappa B; Proteins; Ribonucleases; Time Factors; Transcription Factor AP-1; Transcription, Genetic