Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid Arthritis

Interleukin-10 (IL-10) is a potent deactivator of myeloid cells that limits the intensity and duration of immune and inflammatory responses. The activity of IL-10 can be suppressed during inflammation, infection, or after allogeneic tissue transplantation. We investigated whether inflammatory factors suppress IL-10 activity at the level of signal transduction. Out of many factors tested, only ligation of Fc receptors by immune complexes inhibited IL-10 activation of the Jak-Stat signaling pathway. IL-10 signaling was suppressed in rheumatoid arthritis joint macrophages that are exposed to immune complexes in vivo. Activation of macrophages with interferon-γ was required for Fc receptor–mediated suppression of IL-10 signaling, which resulted in diminished activation of IL-10–inducible genes and reversal of IL-10–dependent suppression of cytokine production. The mechanism of inhibition involved decreased cell surface IL-10 receptor expression and Jak1 activation and was dependent on protein kinase C delta. These results establish that IL-10 signaling is regulated during inflammation and identify Fc receptors and interferon-γ as important regulators of IL-10 activity. Generation of macrophages refractory to IL-10 can contribute to pathogenesis of inflammatory and infectious diseases characterized by production of interferon-γ and immune complexes

Academic emergency medicine physicians\u27 knowledge of mechanical ventilation.

INTRODUCTION: Although emergency physicians frequently intubate patients, management of mechanical ventilation has not been emphasized in emergency medicine (EM) education or clinical practice. The objective of this study was to quantify EM attendings\u27 education, experience, and knowledge regarding mechanical ventilation in the emergency department. METHODS: We developed a survey of academic EM attendings\u27 educational experiences with ventilators and a knowledge assessment tool with nine clinical questions. EM attendings at key teaching hospitals for seven EM residency training programs in the northeastern United States were invited to participate in this survey study. We performed correlation and regression analyses to evaluate the relationship between attendings\u27 scores on the assessment instrument and their training, education, and comfort with ventilation. RESULTS: Of 394 EM attendings surveyed, 211 responded (53.6%). Of respondents, 74.5% reported receiving three or fewer hours of ventilation-related education from EM sources over the past year and 98 (46%) reported receiving between 0-1 hour of education. The overall correct response rate for the assessment tool was 73.4%, with a standard deviation of 19.9. The factors associated with a higher score were completion of an EM residency, prior emphasis on mechanical ventilation during one\u27s own residency, working in a setting where an emergency physician bears primary responsibility for ventilator management, and level of comfort with managing ventilated patients. Physicians\u27 comfort was associated with the frequency of ventilator changes and EM management of ventilation, as well as hours of education. CONCLUSION: EM attendings report caring for mechanically ventilated patients frequently, but most receive fewer than three educational hours a year on mechanical ventilation, and nearly half receive 0-1 hour. Physicians\u27 performance on an assessment tool for mechanical ventilation is most strongly correlated with their self-reported comfort with mechanical ventilation

Academic Emergency Medicine Physicians’ Knowledge of Mechanical Ventilation

Introduction: Although emergency physicians frequently intubate patients, management of mechanical ventilation has not been emphasized in emergency medicine (EM) education or clinical practice. The objective of this study was to quantify EM attendings’ education, experience, and knowledge regarding mechanical ventilation in the emergency department.Methods: We developed a survey of academic EM attendings’ educational experiences with ventilators and a knowledge assessment tool with nine clinical questions. EM attendings at key teaching hospitals for seven EM residency training programs in the northeastern United States were invited to participate in this survey study. We performed correlation and regression analyses to evaluate the relationship between attendings’ scores on the assessment instrument and their training, education, and comfort with ventilation. Results: Of 394 EM attendings surveyed, 211 responded (53.6%). Of respondents, 74.5% reported receiving three or fewer hours of ventilation-related education from EM sources over the past year and 98 (46%) reported receiving between 0-1 hour of education. The overall correct response rate for the assessment tool was 73.4%, with a standard deviation of 19.9. The factors associated with a higher score were completion of an EM residency, prior emphasis on mechanical ventilation during one’s own residency, working in a setting where an emergency physician bears primary responsibility for ventilator management, and level of comfort with managing ventilated patients. Physicians’ comfort was associated with the frequency of ventilator changes and EM management of ventilation, as well as hours of education.Conclusion: EM attendings report caring for mechanically ventilated patients frequently, but most receive fewer than three educational hours a year on mechanical ventilation, and nearly half receive 0-1 hour. Physicians’ performance on an assessment tool for mechanical ventilation is most strongly correlated with their self-reported comfort with mechanical ventilation