Assessing validity and reliability of a new tool: the ECSQ (Endoscopy Customer Satisfaction Question-naire) in Italian for customer satisfaction in digestive endoscopy.

BACKGROUND: The European Society of Gastrointestinal Endoscopy and the American Society for Gastroin-testinal Endoscopy recommend the identification of quality indicators for endoscopy services, including patient satisfaction. Patients happy with the treatment received will be more willing to participate in screening programs and more adherent to the indications received from the doctor. The aim of this study is to validate the Endoscopy Customer Satisfaction Questionnaire in Italian, in order to have a valid and reliable tool that can allow each patient to fully describe their experience in digestive endoscopy services. METHODS: The validation of the questionnaire was carried out through a a monocentric cross-sectional study, in the endoscopy service of the Campus Bio-Medico University Hospital in Rome between August and September 2020. RESULTS: A total of 155 patients underwent an endoscopy. The mean age of the sample was 56.21 years (SD ± 14.136) with 46.5% male and 53.5% female. The analysis of the validity and reliability of the question-naire was ensured through the finding of an average value of 0.944 for Cronbach's α. CONCLUSION: From the analysis of the results, we can therefore believe that the Italian version of the En-doscopy Customer Satisfaction Questionnaire is to be considered valid and reliable for measuring patient satisfaction, allowing them to express their point of view.

The Occupational Health Nurse and his/here role in the prevention of work-related diseases: results of an observational study.

BACKGROUND: In Italy, health in the workplace is still considered a field for physicians only. In contrast to Europe, the figure of the occupational health nurse is not yet present, due to the absences of contractual and university fields. The present study aimed to carry out a survey for understanding the usefulness of the introduction of the occupational health nurse in the field of prevention and protection of health at work. MATERIAL AND METHODS: The questionnaire was administered via an online survey to health professionals including Students (undergraduate and post-graduate levels) of Nursing Sciences and Midwives, Nurses, Physicians specialized in Hygiene and Preventive Medicine, in Occupational Medicine and Legal Medicine. The questionnaire included 26 questions. The statistical analysis, conducted with SPSS software (release 25.0), has been articulated through the use of frequency tables and contingency tables. Differences in participants' responses were analyzed with the chi-square and Fisher's exact tests, where applicable, considering gender, marital status, presence of sons in families, age, macro-region, and professional activities as potential explanatory variables. RESULTS: After two general reminders, 232 individuals entered the survey, with an overall response rate of 65%. 42.2% of the participants were nurses, aged between 20 and 64 years. Around 70% were females. A low percentage (9.9%) is associated with respondents from northern Italy 53.0% from Center and 37.1% from southern Italy. The questionnaire included four major fields of occupational health nursing. The nursing role for companies (items 8, 12, 13, 14, and 17): the responders approve the introduction of the occupational health nurse in the companies for his/her competences on health promotion and work-related diseases prevention. Utility for companies (items 18, 19, 20 and 21): the usefulness brought by the occupational health nurse to companies is fully shared by the responders. Occupational Health Nurse's action field (items 16, 22, 23 and 24): the answer "yes" has the highest prevalence among the responders, followed by "I don't know". Education (items 25 and 26): Nurses, Physicians and Nursing Students think that the occupational health nurse must have an appropriate university training program, in particular, a master's first degree. Concerning the main focus of the study (opinion on which was the most suitable course of study for the occupational health nurse), 85 (36,6 %) participants answered, "First level Master degree", and 60 (25,9 %) "Advanced training course". CONCLUSIONS: This study wanted to highlight the opinion of professionals on the usefulness of this new nursing figure, projected into the world of occupational medicine. The OHN supports the Physician with his/her professionalism and autonomy in prevention and treatment of work-related diseases, as demonstrated and valued in the rest of Europe. The implementation of advanced courses on occupational nursing, and in particular specific post-graduate degrees, is needed.

Role and skills of the oncology nurse: an observational study.

PURPOSE: The importance of nursing competence arises from its central role in influencing and determining care outcomes. The employment of adequately educated staff, able to base clinical decisions on the best scientific evidence, is one of the components required for delivering high quality nursing care in the oncological field. The aim of this study is to analyze - through the Nurse Competence Scale - the level of competence of nurses working in oncological settings. METHOD: A descriptive study was performed between March and September 2017. The participants were recruited among the nursing staff working in the Day Hospital and the Units of the IRCCS -Regina Elena National Cancer Institute in Rome. The confidentiality and the anonymity of the subjects involved in the study were guaranteed by submitting a socio-cultural data sheet -specifically designed to collect demographic and education data - and the Nurse Competence Scale. RESULTS: The sample included 65 nurses (93%) and 5 head nurses (7%), with a mean age of 41.8 years, predominantly female (80%), who had been working in oncology units for a mean of 17.2 years. The Nurse Competence Scale showed a high level of competence in all dimensions. Moreover, the Chi-Square test allowed to identify the presence of significant associations between the different dimensions of the Nurse Competence Scale and the work experience >15 years and the age > 40 years. CONCLUSIONS: The results of our study show that, even if lacking specific oncology competence, nurses working in oncology care settings have developed a good level of clinical competences. Highlighting the importance of nursing care in the oncology area will increase the demand of both patients and organizations of high quality nursing care, consequently enhancing the nursing profession.

Contact precaution procedures in healthcare facilities.

BACKGROUND: Multidrug resistance is an established and growing worldwide public health problem, since few therapeutic options remain available. MRSA is the leading Gram-positive organism which has spread both in the community and healthcare environment. Gram-negative bacteria, either fermenter (enterobacteriaceae) or nonfermenter, pose a major challenge to the healthcare providers because they can express a wide multidrug resistance. METHODS: Specific keywords combinations were analitically searched in PubMed and Scopus databases. Publications concerning contact precaution procedures were reviewed. RESULTS: The review on infection control and isolation precautions was carried out focusing on bundles that could help healthcare personnel to improve their action. CONCLUSIONS: This paper clearly refers to measures in order to control the spread of infectious disease. We provided some synthetic tables that could improve healthcare workers knowledge and help them to apply all fundamental concepts in infection control.

Evaluation of the efficacy of a new oral gel as an adjunct to home oral hygiene in the management of chronic periodontitis. A microbiological study using PCR analysis.

The use of chemical devices for non-surgical periodontal therapy has led to new treatment strategies aiming primarily at infection control and oral bacterial load. Over the last few decades adjunctive chemical devices has been subjected to many scientific and medical studies. The purpose of the present study was to assess the effect of a new oral gel named Parodongel on the red complex organisms using Polymerase Chain Reaction (PCR) for microbiological analysis. A total of 10 patients with a diagnosis of chronic periodontitis in the age group >25 years, were selected. None of these patients had received any surgical or non-surgical periodontal therapy and demonstrated radiographic evidence of moderate bone loss. Four non-adjacent sites in separate quadrants were selected in each patient for monitoring based on criteria that the sites will localize chronic periodontitis. Microbial analysis (MA) was performed at baseline and at day 15. Paired T-Test was used to detect statistical significant reduction of specific bacteria. The results showed statistically significant reduction of the overall bacterial loading and Treponema Denticola from baseline to day 15. Parodongel can be used as an effective local drug delivery together with oral home care in treatment of chronic periodontitis.

Evaluation of the efficacy of a new oral gel containing carvacrol and thymol for home oral care in the management of chronic periodontitis using PCR analysis: a microbiological pilot study.

The use of chemical devices for domestic oral hygiene in periodontal patients has led to new treatment strategies aiming primarily at a control of infection. Over the last few years, carvacrol and thymol (CT) have been subjected to many scientific and medical studies. The purpose of the present study was to assess the effect of CT on the red complex bacteria using Polymerase Chain Reaction (PCR) for microbiological analysis. Five patients with a diagnosis of chronic periodontitis in the age group >25 years, were selected. None of these patients had received any surgical or non-surgical periodontal therapy and demonstrated radiographic evidence of moderate bone loss. After scaling and root planning, patients received a CT gel to be used at home. Four non-adjacent sites in separate quadrants were selected in each patient for monitoring, based on criteria that the sites localize chronic periodontitis. Microbial analysis (MA) was analyzed at baseline and at day 15. SPSS program was used for statistical purposes and a paired samples correlation was performed at the end of the observation period. Although an absolute reduction was observed among the studied bacteria (i.e. Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Campylobacter rectus and Total bacteria loading) none reach a statistical significant value. The present study demonstrated that CT gel has a small impact on oral biofilm. Additional studies are needed to detect the efficacy of CT gel.

The role of hysteroscopy in unexplained infertility.

PURPOSE OF INVESTIGATION: To evaluate pregnancy rate after diagnostic and operative hysteroscopy in nulliparous patients with inter- tility of unknown cause. MATERIALS AND METHODS: The authors conducted this study on 92 nulliparous patients with unexplained infer- tility that underwent diagnostic hysteroscopy which showed an uterine lesion (submucous fibroids, uterine septa, polyps, synechias) and underwent operative hysteroscopy to remove the lesion between 2007 and 2011. Patients' data were retrospectively extrapolated from patient's charts, then the patients were called to ask if they had pregnancies after hysteroscopic surgery. RESULTS: The present study showed a significant increase in pregnancy rate after hysteroscopic surgery (85% during the two years after the surgery). The most common endocavitary lesions were endometrial polyps (21%), uterine septa (25%), and submucous myomas (18%). CONCLUSIONS: Ac- cording to the present data, hysteroscopic evaluation of nulliparous women with unexplained infertility could be useful to detect lesions not diagnosed with other tests, and the treatment of these endocavitary lesions plays an important role in the diagnostic and therapeutic iter. The results show-a pregnancy rate of 85% in the patients treated for endocavitary lesions, but 15% of the patients, despite a normal uterine cavity, continue to have unexplained infertility and are classified as idiopathic infertility.

Validation of a questionnaire for ICU nurses to assess knowledge, attitudes and behaviours towards medication errors.

AIM: Medication errors are dangerous for the patients in an intensive care unit (ICU). Little is known about knowledge, attitudes and professional behaviour of nurses towards prevention of errors and clinical risk management can reduce errors during the preparation and administration phases of intravenous drugs. In this study we have evaluated the reliability and validity of the questionnaire to examine knowledge, attitudes and professional behaviour of ICU nurses. METHODS: Reliability analysis was tested and content validity evaluated using Cronbach's alpha to check internal consistency with the intention to obtain no misunderstanding with the results. The questionnaire composed of seven sections for a total of 36 items, was administrated among ICU nurses working in a university hospital in Rome, Italy. Data were collected in October 2015. Statistical analysis was performed with the statistical software for Windows SPSS, version 22.0. RESULTS: The questionnaire was administered to 30 ICU nurses' in anonymous, voluntary and self-administered form with close-ended type of questions, except for the socio-demographic characteristics. The highest value of Cronbach's alpha resulted on 19 items (alpha= 0,776) meaning that the questionnaire has a satisfactory internal validity. The study highlights that nurses (80%) are aware that appropriate knowledge on the calculation of medication's dose is essential to reduce medication errors during the phase of drugs'preparation. CONCLUSION: This study demonstrated that a short version of the questionnaire has very good reliability properties in the study and this needs to be taken into account for future studies.

Hand hygiene in preventing nosocomial infections:a nursing research.

OBJECTIVES: To verify whether there is some correlation between the nursing workload and the occurrence of healthcare-associated infections. MATERIAL AND METHODS: An anonymous questionnaire made up of 20 items has been drafted for this specific purpose and delivered to a sample of 70 participants, including 33 nurses and 37 nursing students of a well-known University Hospital in Rome. The study is supported by extensive documental research, and a specific literature review. RESULTS: Hand hygiene is a mandatory daily practice, simple but critical, but not always clear enough for both nurses and students. The investigation demonstrated inconsistencies between nurses' and students' behaviour and what is recommended by the new WHO international guidelines. The documented correlation between the workload and the occurrence of healthcare-associated infections may be explained by the negative effect of nursing workload on correct hand-washing procedures. Out of the total sample, 58.6% answered affirmatively to both the presence of healthcare-associated infections within their unit and an excessive daily workload. Indeed, the remaining 41.4% of the sample do not report an excessive workload and states that "there are no healthcare-associated infections within their operational reality, at least not in the time period covered by the present investigation". Although limited to a small sample, this study may reveal that the correct practice of hand washing, prompted and considered fundamental by WHO, is still much underrated. CONCLUSIONS: Hand hygiene should be better understood and practiced in all healthcare facilities, through a series of interventions such as: specific training courses, the presence of a gel sanitizer next to each patient's bed or in each patient's room, as well as the adoption of the new international guidelines in all units. The analysis of other correlations found the presence of a protective factor (RR<1) regarding the replacement of gloves for each patient and the use of disinfectant gel, both related to the excessive workload and the presence of infections. In fact, we found no statistically significant values to support such considerations (p>0.05). The same considerations could be also inferred as far as the presence of gel dispensers and disposable wipes near hospital beds are concerned, for the distribution of information leaflets about proper hand hygiene and the frequency of updating courses declared by both nurses and nursing students. The quality of health care starts from the simplest things, such proper hand hygiene.

Assessment of tetanus immunity status by tetanus quick stick and anamnesis: a prospective double blind study.

BACKGROUND: In patients with wounds admitted to Emergency Departments (ED) acquiring tetanus vaccination history by interview is very unreliable. Protected patients may receive unnecessary prophylaxis and unprotected nothing. Aim of the study was to evaluate tetanus immunity status comparing the traditional anamnestic method with the Tetanus Quick Stick (TQS), a rapid immunochromatographic test. METHODS: A double-blind prospective study was carried out in the ED of the 1,000 bed teaching hospital Umberto I in Rome. Adult patients (≥18) with wounds attending at the ED were randomly included. Tetanus immunity status was evaluated by healthcare workers (HCWs) comparing the TQS test with the anamnesis. TQS test was performed by a trained HCW and afterwards the anamnesis about tetanus immunity status was collected by another HCW unaware of the TQS result. Also cost analysis was carried out. RESULTS: Overall 400 patients (242 males and 158 females) were included, mean age was 46.7 ± 20.2 years (median 44 range 18 - 109), 304 (76.0%) were italians and 96 foreigners (24.0%). Overall, 209 (52.2%) resulted TQS +, and protective immunity level was associated to lower mean age (40.1 ± 16.8 vs 53.8 ± 21,1; p<0,01). Using the anamnestic method 336 (84.0%) patients resulted "unprotected", 52 (13.0%) "partially unprotected" and 12 (3.0%) "completely protected". TQS test results showed that 154 (45.8%) out of 336 "unprotected" and 45 (86.5%) out of 52 "partially unprotected" actually had a protective antibody level. Finally two (16.7%) out of 12 "completely protected" group presented a non protective antibody level. Following only the anamnestic method 201 (50.0%) patients would have received some inappropriate treatment. Adopting TQS test in all patients would also be cost-effective saving € 1.95/patient. As tetanus immunity is inversely related to age, for <51 years old patients unnecessary treatment would have been avoided in 57.1% of patients, with a mean reduction per patient of € 7.50/patient with the TQS vs. € 12.69/patient without. CONCLUSIONS: The study showed that tetanus protective immunity prevalence among adult patients attending our ED is about 50% and is mainly influenced by class age. TQS use allowed to reduce drastically inappropriate tetanus vaccine and immunoglobulins booster treatment. Also TQS use reduced costs.

Social determinants of Health and Google Trends: a worldwide infodemiological report.

OBJECTIVE: Several sociodemographic variables are essential to the complete comprehension of people's health conditions. Also, social determinants of health are decisive in influencing people's health and healthcare strategy outcomes. Nevertheless, the level of awareness of the general population about the social determinants of health still seems poorly investigated. In this scenario, using an infodemiological approach, Google Trends represents a handy tool for monitoring internet-related search activities concerning this specific topic. This study aimed to assess the general population's consciousness about social determinants of health, testing widespread knowledge of these items and evaluating the association of the results obtained through Google-specific search volumes. MATERIALS AND METHODS: Data were collected using the Google Trends tool using several search terms related to food, social problems, and economic issues, which are useful for defining some social determinants of health variables. Descriptive data analysis was performed to show the worldwide Relative Search Volume variations from 1 September 2013 to 31 August 2023. Pearson's correlation analysis tested Relative Search Volumes and later logarithmic transformation. The K-Nearest Neighbors analysis was used to define and assess Relative Search Volumes (RSV) associations. RESULTS: The results have shown that the general population was mainly interested in topics such as "social support" and "economic burden", showing frequent peaks during the 10 years of the study. According to Pearson's coefficients test, other specific interests and relative correlations emerged regarding social variables (i.e., social support and social problems), food, and financial distress. Moreover, the K-Nearest Neighbors analysis showed that searching activities for "social support", "lack of food", and "social problems" were highly related; for "economic burden", "financial burden", and "out of pocket" suggested the existence of financial distress. CONCLUSIONS: The results of this study underline that social determinants of health are significant barriers to health and well-being and that non-medical factors should be considered more. Healthcare professionals involved in public health should study and understand more about the social determinants of health in relation to health outcomes to provide patient-centered care. Finally, this research suggests that we should encourage and maintain a more comprehensive approach to addressing the health needs of patients and communities, also by an infodemiological assessment.

A rapid review of time management strategies among nurse managers.

Background: Time management practice is the act of influencing one's behavioural dimensions to complete as many tasks as possible within a specified amount of time. These behavioural dimensions include work organization and the continued application of time management techniques. Good time management, such as setting goals and priorities, as well as planning and delegating tasks, can facilitate productivity and success, contributing to work effectiveness, maintaining balance and job satisfaction. Conversely, poor time management has been associated with poor quality of work, low productivity, negative influence on the career path, and high levels of stress. Aim: The study aims to identify the strategies used by middle nurse managers in time management. Methods: A rapid review of biomedical databases was undertaken during the month of June 2021. The included studies were published in English and in Italian. Results: Findings reveal that the most used and effective time management strategies for nurse managers are setting goals, and priorities and delegating tasks. Other useful strategies also found to be fundamental are discussed in detail. Conclusion: A manager should prioritize the concept of planning, which can be counted as an efficient time management technique and educate himself on delegating. Time management has an impact not only on productivity and organizational success, but also on the balance between private and working life of managers.

Elderly patients with multimorbidity in the home setting: umbrella review on therapeutic non-adherence causes.

OBJECTIVE: The elderly population is the most at risk regarding adherence, especially in the coexistence of multiple diseases. This study aims to detect factors contributing to therapeutic non-adherence in elderly patients in home settings. MATERIALS AND METHODS: A review protocol was developed to conduct the umbrella review using the methodological framework of the Richardson et al study. The search strategy was developed in December 2022 to conduct a systematic search and to perform an Umbrella Review of systematic reviews, meta-analyses and integrative reviews published from 2012 to 2022 in English. RESULTS: A total of 26,038 articles were identified and screened. 18 relevant articles were included in the study. CONCLUSIONS: Therapeutic adherence in elderly patients with comorbidities in polypharmacotherapy at home is a significant problem in public health and health care. Several factors of non-adherence have been identified in the studies reviewed, confirming that the problem is multifactorial. Reducing the number of medications prescribed would appear optimal, although often not possible, as this has been seen to have an immediate positive impact. A multidisciplinary approach makes it possible not to fragment care, ensuring positive feedback on therapeutic adherence.

Underprescription of medications in older adults: causes, consequences and solutions-a narrative review.

PURPOSE: Under-prescription is defined as the omission of a medication that is indicated for the treatment of a condition or a disease, without any valid reason for not prescribing it. The aim of this review is to provide an updated overview of under-prescription, summarizing the available evidence concerning its prevalence, causes, consequences and potential interventions to reduce it. METHODS: A PubMed search was performed, using the following keywords: under-prescription; under-treatment; prescribing omission; older adults; polypharmacy; cardiovascular drugs; osteoporosis; anticoagulant. The list of articles was evaluated by two authors who selected the most relevant of them. The reference lists of retrieved articles were screened for additional pertinent studies. RESULTS: Although several pharmacological therapies are safe and effective in older patients, under-prescription remains widespread in the older population, with a prevalence ranging from 22 to 70%. Several drugs are underused, including cardiovascular, oral anticoagulant and anti-osteoporotic drugs. Many factors are associated with under-prescription, e.g. multi-morbidity, polypharmacy, dementia, frailty, risk of adverse drug events, absence of specific clinical trials in older patients and economic factors. Under-prescription is associated with negative consequences, such as higher risk of cardiovascular events, worsening disability, hospitalization and death. The implementation of explicit criteria for under-prescription, the use of the comprehensive geriatric assessment by geriatricians, and the involvement of a clinical pharmacist seem to be promising options to reduce under-prescription. CONCLUSION: Under-prescription remains widespread in the older population. Further studies should be performed, to provide a better comprehension of this phenomenon and to confirm the efficacy of corrective interventions.

Impact of nursing students on the quality of care perceived by patients: a systematic review of the literature.

OBJECTIVE: The quality assessment process, based on customer satisfaction, is fundamental in the delivery of the best care services. This is most evident in care settings where trainee students are allowed to assist the patients. The purpose of this review is to clarify whether nursing students have an impact on patients' assessment of the quality of their nursing care. MATERIALS AND METHODS: A systematic literature search was carried out using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines in six databases: PubMed, CINAHL, Cochrane, Web of Science, Scopus, and PsycInfo. Two co-authors independently screened titles, abstracts, and full-text articles, following explicit exclusion and inclusion criteria. Analyses included non-randomized and non-homogeneous samples, involving both selected patients and methods for assessing their satisfaction. RESULTS: After full-text screening, 30 articles were identified, but only 11 were considered pertinent to the topic of the review. The trainee-patient relationship is based on mutual help and can improve the patient experience and trainee learning. The instruments used to measure perceived quality were found to be valid and reliable. CONCLUSIONS: The studies under review show high levels of satisfaction among patients when nursing care is delivered through training, particularly when the patients who agree to be treated by nursing trainees have previous experience of hospitalization and relationships with trainees. Educational background and the empathy and communication skills of both professional nurses and trainees influence patients' perception of the quality of care and their satisfaction with it.

Comparison across 12 countries on knowledge, attitude, and behavior scores about medication errors in Intensive Care Units: an international study.

OBJECTIVE: The aim of the study was to explore the degree of agreement of intensive care unit nurses working on a set of medication error preventive strategies and to examine possible predictors of nurses' knowledge, attitude and behavior. MATERIALS AND METHODS: Observational, international, and cross-sectional study. Iran, Malta, Spain, Pakistan, Nepal, Qatar, Ecuador, Australia, Finland, Italy, Egypt, and Jordan were the countries included in this survey. To collect data, the Knowledge, Attitude and Behavior in Medication Errors questionnaire was used. A descriptive statistical analysis was performed for the socio-demographic characteristics of the sample and three multiple logistic regressions were performed. RESULTS: The international sample consists of 1383 nurses, of whom 478 (34.6%) were men and 900 (65.1%) were women and their mean age was 35.61 years with a range of 19-61. Descriptive statistics conducted on the international sample show a medium to high degree of agreement among participants concerning some preventive strategies of medication error. In addition, the results of the present study show a strong relationship between positive nurses' attitudes and correct behaviors and/or adequate knowledge, as well as between adequate knowledge and correct behaviors (p< 0.01). CONCLUSIONS: Further studies are needed to explore the issue of medication error concerning nurses' cultural backgrounds, as well as to assess similarities and disparities among international nurses.

The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6).

The human homologue of Drosophila Toll (hToll) is a recently cloned receptor of the interleukin 1 receptor (IL-1R) superfamily, and has been implicated in the activation of adaptive immunity. Signaling by hToll is shown to occur through sequential recruitment of the adapter molecule MyD88 and the IL-1R-associated kinase. Tumor necrosis factor receptor-activated factor 6 (TRAF6) and the nuclear factor kappaB (NF-kappaB)-inducing kinase (NIK) are both involved in subsequent steps of NF-kappaB activation. Conversely, a dominant negative version of TRAF6 failed to block hToll-induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases, thus suggesting an early divergence of the two pathways.

The type II "receptor" as a decoy target for interleukin 1 in polymorphonuclear leukocytes: characterization of induction by dexamethasone and ligand binding properties of the released decoy receptor.

Whereas the signaling function of the interleukin 1 (IL-1) receptor type I (IL-1R I) has been well documented, the type II "receptor" has been suggested to act as a decoy target for this cytokine. Since IL-1 may represent a key target of the immunomodulatory and antiinflammatory properties of glucocorticoids (GC), the aim of this study was to investigate the effects of dexamethasone (Dex) on IL-1R expression in human polymorphonuclear leukocytes (PMN), which express predominantly the type II molecule (IL-1R II). We found that Dex augments the levels of steady state transcripts encoding the IL-1R I and, most prominently, those of IL-1R II. Dex induced both transcripts via transcription-dependent mechanisms and by prolongation of the mRNAs half-lives. Inhibition of protein synthesis superinduced basal and Dex-augmented IL-1R II mRNA, whereas it completely inhibited the induction by Dex of IL-1R I transcripts. Induction of IL-1R II mRNA by Dex was associated with augmented membrane expression and release of the type II IL-1 binding molecule. This effect was mediated by the GC receptor. Other steroids (17 beta-estradiol, progesterone, and testosterone) were ineffective. The concentrations of IL-1 alpha and IL-1 receptor antagonist required to displace the binding of IL-1 beta to the soluble form of the decoy molecule induced by Dex from PMN were, respectively, 100 and 2 times higher compared with IL-1 beta. The induction by Dex of the type II receptor, a decoy molecule for IL-1, may contribute to the immunosuppressive and antiinflammatory activities of Dex.

Cloning and characterization of a new isoform of the interleukin 1 receptor antagonist.

By reverse transcriptase polymerase chain reaction on messenger RNA from human polymorphonuclear cells, we have isolated a sequence identical to the cDNA coding for intracellular interleukin 1 receptor antagonist (icIL-1ra), but containing an additional in-frame 63-bp sequence located three codons downstream of the translation start of icIL-1ra. This additional sequence is inserted between the first and second exon of the intracellular form, the latter of which is colinear with part of the first exon of the secreted form of IL-1ra. The additional sequence is coded by an extra exon located 2 kb downstream the first icIL-1ra-specific exon. The complementary DNA sequence of the alternatively spliced form of icIL-1ra shows that the predicted protein differs from classical icIL-1ra in the NH2 terminus by insertion of a leaderless sequence of 21 amino acids rich in glycine and glutamic acid residues. Transcripts coding for this new form of icIL-1ra were detected in activated fibroblasts, keratinocytes, and at low levels in myelomonocytic cells. The recombinant protein expressed in COS cells had an apparent molecular mass in sodium dodecyl sulfate polyacrylamide gel electrophoresis of 25 kD compared to 22 kD of classical icIL-1ra, and was mostly intracellular. The ability of this new form of icIL-1ra to inhibit IL-1 activity, in terms of induction of E-selectin and human immunodeficiency virus replication, was comparable to that of classical icIL-1ra. We propose to refer to this new form of icIL-1ra as icIL-1ra type II.

Inhibition of interleukin-1 responsiveness by type II receptor gene transfer: a surface "receptor" with anti-interleukin-1 function.

The hypothesis that the type II receptor (RII) acts as a decoy for interleukin-1 (IL-1) was tested by gene transfer in cells expressing only the type I receptor (8387 fibroblasts). RII-transfected cells showed defective responsiveness to IL-1 in terms of NFkappaB activation, cytokine gene expression and production. Blocking monoclonal antibodies against RII restored the capacity of RII-transfected cells to respond to IL-1 beta. Hence defective IL-1 responsiveness of RII-transfected cells requires surface expression of the molecule. RII-transfected cells showed normal responsiveness to TNF, which shares functional properties and elements in the signal transduction pathway with IL-1. Cells transfected with a deletion mutant of RII missing 26 of 29 amino acids of the cytoplasmic portion of the molecule showed impaired responsiveness to IL-2. Cells transfected with full-length or the cytoplasmic deletion mutant of RII released copious amounts of RII in the supernatant. However, transfected cells showed defective responsiveness to brief exposure to IL-1, in the absence of measurable released RII. These results indicate that impairment of the responsiveness to IL-1 following RII gene transfer was dependent upon surface expression of the molecule, specific for IL-1 and unaffected by truncation of the cytoplasmic portion. Thus, the type II "receptor" is a decoy surface molecule, regulated by antiinflammatory signals, whose only known function is to capture and block IL-1.