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Biomedical subjects

Paul van Cauwenberge

Publications and source records attributed to Paul van Cauwenberge.

10 recordsLinked to original sources
PubMed2006

Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps is characterized by an eosinophilic inflammation and high IL-5 levels. OBJECTIVES: Antagonizing the effect of IL-5 is a potential new treatment strategy in patients with nasal polyps. METHODS: In a double-blind, placebo-controlled, randomized, 2-center safety and pharmacokinetic study, 24 subjects with bilateral nasal polyps were randomized to receive a single intravenous infusion of reslizumab, a humanized anti-human IL-5 mAb, at 3 mg/kg or 1 mg/kg or placebo. We evaluated the safety and pharmacokinetics of reslizumab, and biologic activity was assessed by means of endoscopic evaluation of polyp size, symptoms, peripheral eosinophil counts, peripheral and local IL-5 levels, eotaxin levels, and eosinophil cationic protein levels. RESULTS: We demonstrated that a single injection of reslizumab up to 3 mg/kg is safe and well tolerated. Blood eosinophil numbers and concentrations of eosinophil cationic protein were reduced up to 8 weeks after treatment in serum and nasal secretions. Individual nasal polyp scores improved only in half of the treated patients for 4 weeks. Responders had increased IL-5 concentrations in nasal secretions at baseline compared with nonresponders, and logistic regression analysis revealed that increased nasal IL-5 levels (>40 pg/mL) predict the response to anti-IL-5 treatment. CONCLUSION: A single injection of anti-IL-5 reduces the size of nasal polyps for 4 weeks in half of the patients, and nasal IL-5 levels predict the response to anti-IL-5 treatment. CLINICAL IMPLICATIONS: Intravenous administration of a humanized anti-human IL-5 mAb is safe and reduces the size of nasal polyps in half of the patients.

Adolescent↗
PubMed2006

Expression of nicotinic acetylcholine receptor subunit alpha9 in type II vestibular hair cells of rats.

AIM: To explore the cell specific existence of alpha 9 AChR in the vestibular type II hair cells (VHC II) of rats. METHODS: To detect the expression of alpha 9 AChR messenger RNA (mRNA) in the vestibular endorgans and single VHC II of rats by using the reverse transcription polymerase chain reaction (RT-PCR) technique and the single cell RT-PCR technique, respectively. RESULTS: It was shown that alpha 9 AChR mRNA was detected in the vestibular endorgans. By using single-cell RT-PCR, mRNA encoding alpha 9 AChR was also detected in the VHC II of the rats. Sequence analysis of the PCR products confirmed identity to corresponding cDNA sequence in the predicted region. CONCLUSION: We established a method which could effectively detect the cell specific expression of mRNA in an individual VHC. Present data confirm that alpha 9 AChR mRNA is expressed in the VHC II of rats and indicates that alpha 9 AChR may function as a mediator of efferent cholinergic signaling in mammalian VHC.

Animals↗
PubMed2004

Aspirin sensitivity and IgE antibodies to Staphylococcus aureus enterotoxins in nasal polyposis: studies on the relationship.

BACKGROUND: Nasal polyposis is a multifactorial disease characterized by a chronic eosinophilic inflammation of the sinus mucosa, often associated with asthma and aspirin sensitivity. We have recently shown that the presence of IgE antibodies to Staphylococcus aureus enterotoxins (SAEs) was related to the severity of eosinophilic inflammation in nasal polyp tissue. In this study, we therefore aimed to determine, whether aspirin sensitivity was related to an immune response to SAEs, and how both criteria would be related to eosinophilic inflammation. METHODS: 40 subjects with nasal polyposis (NP) were classified as aspirin-sensitive (n=13, ASNP) or aspirin-tolerant (n=27, ATNP) based on a bronchial aspirin challenge test. Homogenates prepared from nasal polyp tissue and inferior nasal turbinates from healthy subjects (n=12) were analyzed for concentrations of IL-5 by enzyme immunoassay and for ECP, total and IgE to a mix of SAEs (A, C, TSST-1) using the ImmunoCAP system. RESULTS: Concentrations of IL-5, ECP, total IgE, and IgE to an SAE mix were significantly increased in ASNP compared with ATNP patients and controls. In addition, a subgroup analysis showed an increase in eosinophilic markers in ATNP-SAE(+) compared to ATNP-SAE(-). This relationship, however, was not found in ATNP-SAE(+) and ATNP-SAE(-) subjects, indicating that SAE immune response is overlapped or not relevant in this condition. CONCLUSIONS: Aspirin sensitivity was associated with increased concentrations of eosinophil-related mediators, as well as IgE antibodies to SAEs in nasal polyp tissue. However, a direct impact of S. aureus could not be established. It seems that aspirin sensitivity and immune reactions to SAEs are independently related to eosinophilic inflammation.

Adult↗
PubMed2002

Secretion of TGF-betal, TGF-beta2, EGF and PDGF into nasal fluid after sinus surgery.

Wound healing is a highly coordinated process involving clot formation, inflammatory reaction, immune response and tissue remodeling. The transforming growth factor beta (TGF-beta), epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) are known to be active during different phases of wound repair. The authors postulated that changes in the spontaneous secretion of these growth factors could be detected in nasal fluid after sinus surgery and propose a standardized technique to follow the healing process. The study was designed as a single-center prospective pilot study. Nasal secretions were obtained from eight patients at 1, 2 and 3 weeks after functional endoscopic sinus surgery (FESS) and compared to 13 controls. Nasal fluid was collected by sinus packing and was analyzed by ELISA for TGF-betal, TGF-beta2, EGF and PDGF. Comparing patients at 1 week after surgery with control subjects, a significant increase in the concentrations of TGF-betal, TGF-beta2 and PDGF in nasal secretions could be demonstrated ( P<0.001). At 2 and 3 weeks after surgery, decreasing amounts of these growth factors were found, nearly reaching normal conditions again. This decrease was not significant between visits. In contrast, EGF concentrations in nasal fluids tended to have decreased in patients 1 week after FESS compared to controls, with this level persisting during 3 weeks of mucosal healing. This is the first study proposing a follow-up method for nasal and sinus mucosal healing after surgery in order to determine cytokine secretion profiles.

Adult↗
PubMed2002

Staphylococcus aureus superantigens and airway disease.

Twenty-five percent of the population are permanent carriers of Staphylococcus aureus, possibly producing a variety of toxins with superantigenic properties. Staphylococcal superantigens are a group of high- molecular-weight pyrogenic proteins that have in common an extremely potent stimulatory activity for T-lymphocytes, macrophages, mast cells, eosinophils, and epithelial cells. The role of staphylococcal superantigens in atopic dermatitis has recently been recognized, and new evidence suggests that similar mechanisms may also be relevant in airway disease. This circumstantial evidence is currently limited to rhinitis, sinusitis, and possibly asthma, but may, if supported, open a new understanding of pathomechanisms and therapeutic targets.

Allergens↗
PubMed2002

Mediators in nasal polyposis.

Nasal polyposis (NP) is a chronic inflammatory disease of the sinuses often associated with asthma. Although we have not yet achieved a full understanding of the precise mechanisms underlying the pathogenesis of NP, recent insights have been acquired into the regulation of eosinophil chemotaxis, activation, and survival, in addition to their possible link to gross histopathologic changes such as pseudocyst formation. Interleukin (IL)-5, transforming growth factor-beta(1), and eotaxin seem to be crucial players in the regulation of eosinophilic inflammation and extracellular matrix breakdown. The cytokine pattern in NP assumes neither a T helper 1 (Th1) nor Th2 type predominance, because IL-4, IL-5, IL-12, and interferon-gamma have all been shown to be upregulated in NP tissue, without influence of the atopic status. However, recent studies have demonstrated a strong local upregulation of the immunoglobulin E (IgE) synthesis with the formation of specific IgE to Staphylococcus aureus enterotoxins, suggesting a possible role of superantigens in these pathologic processes.

Cell Adhesion Molecules↗
PubMedDate not supplied

Pattern of inflammation and impact of Staphylococcus aureus enterotoxins in nasal polyps from southern China.

BACKGROUND: This study analyzes the impact of Staphylococcus aureus enterotoxins (SAEs) and the inflammatory pattern in polyps from China. METHODS: Nasal tissue was obtained from 27 consecutive bilateral nasal polyps and 15 control patients and assayed for eotaxin, interleukin-5, soluble interleukin-2 receptor, transforming growth factor (TGF) beta, myeloperoxidase, eosinophil cationic protein, total IgE, and specific IgE to SAEs. Activated eosinophils were stained using EG2 antibodies in polyps from Chinese and comparative white patients. RESULTS: The number of EG2+ eosinophils was significantly lower in polyps from Chinese patients versus white patients. Chinese polyps showed significantly increased IgE and soluble interleukin-2 receptor versus control samples, whereas TGF-beta1 was significantly decreased. Ten of 27 samples in the polyp group versus 0 of 15 controls contained SAE-IgE (p < 0.01). TGF-beta1 was significantly down-regulated in SAE+ samples versus SAE- samples (p = 0.04). CONCLUSION: Nasal polyps from China are characterized by B- and T-cell activation, a minor eosinophilic inflammation compared with polyps from white subjects, and a decrease in TGF-beta1 in comparison with control inferior turbinate tissue. One-third of patients with polyps showed an IgE response to SAEs.

Adolescent↗