interleukin-8 and Cystitis--Interstitial

Interstitial cystitis (IC) has a chronic chemical irritation and inflammation of non-bacterial origin in the bladder wall leading to various severe symptoms. There is evidence that chronic inflammation is significantly associated with abnormal urothelial barrier function, epithelial dysfunction. This is the underlying cause of urothelial apoptosis and sterile inflammation.. The anti-inflammatory effects of lavender and eucalyptus essential oils (EOs) and their main components (linalool and eucalyptol) were investigated in the T24 human bladder epithelial cell line on TNFα stimulated inflammation, at 3 types of treatment schedule. The mRNA of pro-inflammatory cytokines (IL-1β, IL-6, IL-8) were measured by Real Time PCR. Human IL-8 ELISA measurement was performed as well at 3 types of treatment schedule. The effects of lavender and eucalyptus EOs and their main components were compared to the response to NFκB inhibitor ACHP (2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3-pyridinecarbonitrile).. There is no significant difference statistically, but measurements show that lavender EOs are more effective than eucalyptus EO. Long time treatment (24 h) of both lavender EO and linalool showed higher effect in decreasing pro-inflammatory cytokine mRNA expression than ACHP inhibitor following TNFα pre-treatment. Moreover, both lavender EOs were found to be significantly more effective in decreasing IL-8 secretion of T24 cells after TNFα pre-treatment compared to the ACHP NFκB-inhibitor.. The lavender EOs may be suitable for use as an adjunct to intravesical therapy of IC. Their anti-inflammatory effect could well complement glycosaminoglycan-regenerative therapy in the urinary bladder after appropriate pharmaceutical formulation.

Topics: Anti-Inflammatory Agents; Cell Culture Techniques; Cystitis, Interstitial; Cytokines; Eucalyptus; Female; Humans; Inflammation; Interleukin-8; Lavandula; Male; Oils, Volatile; RNA, Messenger; Tumor Necrosis Factor-alpha

This study investigated the usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We retrospectively enrolled 315 patients (267 women and 48 men) diagnosed with IC/BPS and 30 controls. Data on clinical and urodynamic characteristics (visual analog scale (VAS) score and bladder capacity) and cystoscopic hydrodistention findings (Hunner's lesion, glomerulation grade, and maximal bladder capacity (MBC)) were recorded. Urine samples were utilized to assay inflammatory, neurogenic, and oxidative stress biomarkers, including interleukin (IL)-8, C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), eotaxin, IL-6, macrophage inflammatory protein 1 beta (MIP-1β), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-isoproatane, and total antioxidant capacity. Further, specific histopathological findings were identified via bladder biopsy. The associations between urinary biomarker levels and bladder conditions and histopathological findings were evaluated. The results reveal that patients with IC/BPS had significantly higher urinary MCP-1, eotaxin, TNF-α, PGE2, 8-OHdG, and 8-isoprostane levels than controls. Patients with Hunner's IC (HIC) had significantly higher IL-8, CXCL10, BDNF, eotaxin, IL-6, MIP-1β, and RANTES levels than those with non-Hunner's IC (NHIC). Patients with NHIC who had an MBC of ≤760 mL had significantly high urinary CXCL10, MCP-1, eotaxin, IL-6, MIP-1β, RANTES, PGE2, and 8-isoprostane levels and total antioxidant capacity. Patients with NHIC who had a higher glomerulation grade had significantly high urinary MCP-1, IL-6, RANTES, 8-OHdG, and 8-isoprostane levels. A significant association was observed between urinary biomarkers and glomerulation grade, MBC, VAS score, and bladder sensation. However, bladder-specific histopathological findings were not well correlated with urinary biomarker levels. The urinary biomarker levels can be useful for identifying HIC and different NHIC subtypes. Higher urinary inflammatory and oxidative stress biomarker levels are associated with IC/BPS. Most urinary biomarkers are not correlated with specific bladder histopathological findings; nevertheless, they are more important in the assessment of bladder condition th

Topics: 8-Hydroxy-2'-Deoxyguanosine; Antioxidants; Biomarkers; Brain-Derived Neurotrophic Factor; Chemokine CCL2; Chemokine CCL4; Chemokine CCL5; Cystitis, Interstitial; Dinoprostone; Female; Humans; Interleukin-6; Interleukin-8; Ligands; Male; Retrospective Studies; Tumor Necrosis Factor-alpha; Urinary Bladder

Interstitial cystitis/bladder pain syndrome (IC) is a multifactorial syndrome of severe pelvic and genitalia pain and compromised urinary function; a subset of IC patients present with Hunner's lesions or ulcers on their bladder walls (UIC). UIC is diagnosed by cystoscopy, which may be quite painful. The objective of this study was to determine if a calculated Bladder Permeability Defect Risk Score (BP-RS) based on non-invasive urinary cytokines could discriminate UIC patients from controls and IC patients without Hunner's ulcers.. A national crowdsourcing effort targeted IC patients and age-matched controls to provide urine samples. Urinary cytokine levels for GRO, IL-6, and IL-8 were determined using a Luminex assay.. We collected 448 urine samples from 46 states consisting of 153 IC patients (147 female, 6 male), of which 54 UIC patients (50 females, 4 male), 159 female controls, and 136 male controls. A defined BP-RS was calculated to classify UIC, or a bladder permeability defect etiology, with 89% validity.. The BP-RS Score quantifies UIC risk, indicative of a bladder permeability defect etiology in a subset of IC patients. The Bladder Permeability Defect Risk Score is the first validated urine biomarker assay for interstitial cystitis/bladder pain syndrome.

Topics: Adult; Case-Control Studies; Chemokine CXCL1; Cystitis, Interstitial; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Permeability; Risk

Hyaluronic acid (HA) has received a lot of attention recently as a biomaterial with applications in wound healing, drug delivery, vascular repair and cell and/or gene delivery. Interstitial cystitis (IC) is characterised by an increase in the permeability of the bladder wall urothelium due to loss of the glycosaminoglycan (GAG) layer. The degradation of the urothelium leads to chronic pain and urinary dysfunction. The aetiology of the degradation of the GAG layer in this instance is currently unknown. At a clinical level, GAG replacement therapy using a HA solution is currently utilised as a treatment for IC. However, there is a significant lack of data on the mechanism of action of HA in IC. The current study investigates the mechanistic effect of clinically relevant HA treatment on an in vitro model of IC using urothelial cells, examining cytokine secretion, GAG secretion and trans-epithelial permeability. This study demonstrates that HA can significantly decrease induced cytokine secretion (4-5 fold increase), increase sulphated GAG production (2-fold increase) and without altering tight junction expression, decrease trans-epithelial permeability, suggesting that the HA pathway is a clinical target and potential treatment vector.

Topics: Cell Membrane Permeability; Cystitis, Interstitial; Dose-Response Relationship, Drug; Glycosaminoglycans; Humans; Hyaluronic Acid; Interleukin-6; Interleukin-8; Materials Testing; Tight Junctions; Urothelium

Interleukin-8 (IL-8; CXCL8) has been shown to play a role in multiple cellular processes. Here, we report an additional role of IL-8 as a growth and essential survival factor for normal human urothelial cells. Supplementing exogenous recombinant human IL-8 to normal urothelial cells promoted cell growth through the Akt pathway. Inhibition of IL-8 expression by small inhibitory RNA (siRNA) caused normal urothelial cells to die. Addition of recombinant human IL-8 rescued the normal urothelial cells treated with IL-8 siRNA. This rescue effect could be blocked by antibodies to the IL-8 receptor CXCR1 but not by CXCR2, suggesting that normal urothelial cells normally have IL-8 autocrine or paracrine activity for survival and growth mediated by CXCR1. IL-8 mRNA levels were lower in samples from patients with interstitial cystitis, a urinary bladder disorder associated with urothelial cell dysfunction and/or loss. Taken together, these results suggest that IL-8 is an important normal urothelial growth factor and is necessary for normal urothelial cell survival in vitro and in vivo. Lower IL-8 expression levels in the urinary bladder may contribute to pathophysiology of interstitial cystitis.

Topics: Cell Proliferation; Cell Survival; Cells, Cultured; Cystitis, Interstitial; Humans; Interleukin-8; Proto-Oncogene Proteins c-akt; Receptors, Interleukin-8A; Recombinant Proteins; RNA Interference; RNA, Messenger; Signal Transduction; Time Factors; Ureter; Urinary Bladder; Urothelium

Topics: Biomarkers; Chemokine CCL2; Chronic Disease; Cystitis, Interstitial; Humans; Interleukin-8; Macrophage Inflammatory Proteins; Mast Cells; Pelvic Pain; Urinary Bladder; Urinary Bladder Diseases

We tested for associations between urine markers, bladder biopsy features and bladder ulcers in interstitial cystitis/painful bladder syndrome.. Subjects were 72 patients with interstitial cystitis/painful bladder syndrome undergoing bladder distention and biopsy. Urine was collected before the procedure. Urine marker levels were correlated with biopsy and cystoscopic findings. Patients with no previous interstitial cystitis/painful bladder syndrome treatments (47) were analyzed separately from previously treated patients (25).. For untreated patients urine interleukin-6 and cyclic guanosine monophosphate were associated with urothelial epidermal growth factor receptor staining (for interleukin-6 r = 0.29; 95% CI 0.07, 0.51; p = 0.01 and for cyclic guanosine monophosphate r = 0.34; 95% CI 0.13, 0.55; p = 0.002). Urine interleukin-8 was negatively associated with urothelial heparin-binding epidermal growth factor-like growth factor staining (r = -0.34; 95% CI -0.55, -0.12; p = 0.002) and positively associated with lamina propria mast cell count (r = 0.29; 95% CI 0.06, 0.52; p = 0.01). The latter association also was seen in treated patients (r = 0.46; 95% CI 0.20, 0.73; p <0.001). None of the urine markers was significantly different for ulcer vs nonulcer groups. All of the patients with ulcer had extensive inflammation on bladder biopsy including severe mononuclear cell infiltration, moderate or strong interleukin-6 staining in the urothelium and lamina propria, and leukocyte common antigen staining in more than 10% of the lamina propria. However, these features also were seen in 24% to 76% of the patients without ulcer.. Overall urine markers did not associate robustly with biopsy findings. The strongest association was a positive association between urine interleukin-8 levels and bladder mast cell count. Patients with ulcer consistently had bladder inflammation but the cystoscopic finding of ulcers was not a sensitive indicator of inflammation on bladder biopsy.

Topics: Adult; Aged; Biomarkers; Biopsy, Needle; Cyclic GMP; Cystitis, Interstitial; ErbB Receptors; Female; Glycoproteins; Heparin-binding EGF-like Growth Factor; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Interleukin-6; Interleukin-8; Male; Mast Cells; Middle Aged; Ulcer; Urinary Bladder; Urinary Bladder Diseases; Urothelium

A middle-aged woman with lupus cystitis showed no other symptoms of lupus vasculitis. Cystoscopic findings revealed mucosal hemorrhage and hyperemia. Histological studies of the bladder showed mucosal edema, inflammatory cellular infiltration and the deposition of immune complexes along the vessels. She was treated with a combination of intravenous methylprednisolone pulse therapy and oral prednisolone. Cystoscopy and histological findings showed appreciable improvement. Elevated urinary levels of chemokines such as interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF) decreased during convalescence. These results suggest that the early diagnosis and treatment with steroid pulse therapy achieves improvement of an unusual vasculitis symptom, lupus cystitis.

Topics: Anti-Inflammatory Agents; Chemokine CCL2; Cystitis, Interstitial; Drug Therapy, Combination; Edema; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Lupus Erythematosus, Systemic; Methylprednisolone; Middle Aged; Mucous Membrane; Prednisolone; Urinary Bladder Diseases