Immune system kick-started in moist nasal lining in sinusitis, asthma and coldsApril 30, 2008Study explains why steroid therapy loses its punch over time Scientists at Johns Hopkins have outlined a new path for potential therapies to combat inflammation associated with sinusitis and asthma based on a new understanding of the body's earliest immune response in the nose and sinus cavities. Researchers say their findings, to be published in the May edition of the Journal of Allergy and Clinical Immunology, are the first evidence describing how viral agents, such as the rhinovirus responsible for the common cold, can kick start the body's mobilization of immune white blood cells in the moist, mucous membrane lining of the nasal passages. While such responses are key to maintain health in the face of pathogens, they can also become a source of illness due to resulting inflammation. This can lead to potentially life-long problems, including tissue swelling, nasal polyp formation, sneezing, stuffy and runny nose, sore throat, cough, headache, chills, fever and difficulty breathing. Thus, blocking these reactions, the researchers point out, could interrupt the cascade of feel-awful symptoms that ensue. The focus of the study is B7-related proteins, called B7 homologs, which trip white blood cell response in a pathogen attack. Using purified cold virus and its genetic material as bait, the scientists found that production of two B7 homologs spiked in response: Levels of B7-H1 jumped almost ninefold and levels of B7-DC tripled. Until now, says senior study investigator Jean Kim, M.D., Ph.D., viruses were known to reside in and infect the physical epithelium, invading surface membrane cells and revving up the immune system's main blood cell defenses, "but no one knew the major steps involved in or precisely how this immune response was triggered." "The inside surface of our nose and sinuses is much more than a protective cover, and we have good scientific evidence to show that epithelial cells on these mucosal membranes are very powerful mediators - middlemen - in diseases that result in inflammation," adds Kim. An assistant professor at the Johns Hopkins University School of Medicine and an expert in the molecular origins of inflammation, Kim is also an authority on nasal and sinus infections. Moreover, Kim notes, study results demonstrate how the body's immune system is interconnected, where one key part, the physical lining that filters out and captures invading viruses and environmental allergens, can trigger the other key part, which leads to targeted white blood cell action. "Now that we have a better understanding of the immune pathway, we can start to develop therapies that could potentially block the triggering reactions for sinusitis and asthma, which are both made worse when people are infected with the common cold virus," she says. Sinusitis is the most common respiratory complaint in the United States. The condition is often linked with asthma, which affects more than 30 million, including 9 million children. Each year, 62 million Americans catch a cold. The study also explains a common failure in current therapy. According to Kim, nasal and oral steroids are frequently prescribed for many of the 15 percent of the American adult population who suffer from sinusitis, nasal polyps or asthma. Steroids complement drugs taken for symptomatic relief, such as decongestants and pain relievers. But corticosteroid drugs, she says, do not work for everyone and their effectiveness often wanes over time. This may be related to the B7 homolog triggers in the mucous membranes, Kim says, as study results showed that corticosteroid therapy does not fully shut down or prevent their overproduction. In the study's first set of experiments, researchers found that levels of two of five key proteins tested, B7-H1 and B7-DC, rose sharply after samples of nasal cell concentrate were exposed to genetic material from cold viruses. Spiked production was detected using antibodies chemically tagged to glow when bonded to a specific B7 homolog. However, when researchers pretreated the cell scrapings with a well-known anti-inflammatory corticosteroid, called flucticasone propionate, the drug failed to stop overproduction of either B7-H1 or B7-DC. In the final set of study experiments, six adult volunteers were infected with the cold virus and monitored for variations in their immune response during infection, which typically lasts a week to 10 days. Analysis of daily scrapings of surface cells lining the nose showed that production of B7-H1 and B7-DC peaked on the second and third days, when cold symptoms were also at their worst. These protein levels, as a measure of severity of the immune response, dropped quickly afterwards, and at the same time as scores of symptom severity went down. It was this evidence that verified the triggering connection between the cold virus and the immune white cell response inside the nose and sinuses, says Kim. Kim says that researchers' next steps are to analyze the biological control mechanisms for producing the B7 homologs in the nasal lining, and to map out any chemical interactions that result, to look for ways of breaking the cycle of inflammation involved in sinusitis, asthma and colds. Johns Hopkins Medical Institutions |
|||||||||||||||||||||
| Related Sinusitis Current Events and Sinusitis News Articles Johns Hopkins researchers track down protein responsible for chronic rhinosinusitis with polyps A protein known to stimulate blood vessel growth has now been found to be responsible for the cell overgrowth in the development of polyps that characterize one of the most severe forms of sinusitis, a study by Johns Hopkins researchers suggests. Patients with chronic rhinosinusitis have increased incidence of other chronic illnesses Patients who suffer from chronic rhinosinusitis (CRS) also tend to suffer from other chronic illnesses, like asthma, hypertension, and arthritis. Safety, efficacy of corneal transplant procedure confirmed; an antibiotic can cause double vision Highlights of September's Ophthalmology, the journal of the American Academy of Ophthalmology (Academy), include a 2009 review by the Academy of the safety and efficacy of a widely used corneal transplant procedure and a warning about an unusual but serious reaction to systemic fluroquinolones, a class of antibiotics used to treat a variety of bacterial infections. Misuse of common antibiotic is creating resistant TB Use of a common antibiotic may be undercutting its utility as a first-line defense against drug-resistant tuberculosis (TB). Fluoroquinolones are the most commonly prescribed class of antibiotics in the U.S. and are used to fight a number of different infections such as sinusitis and pneumonia. Waist size and body mass index are risk factors for sleep disordered breathing in children A study in the June 1 issue of the journal SLEEP found that waist circumference and body mass index (BMI) are consistent, independent risk factors for all severity levels of sleep disordered breathing (SDB) in children, suggesting that as with adult SDB, metabolic factors are important risk factors for childhood SDB. Of Mice and Peanuts: A new mouse model for peanut allergy Chicago researchers report the development of a new mouse model for food allergy that mimics symptoms generated during a human allergic reaction to peanuts. Is ineffective esophageal motility associated with gastropharyngeal reflux disease? IEM is associated with an increased acid clearance times in the distal esophagus. Gastropharyngeal reflux causes supraesophageal manifestations such as globus, chronic cough, hoarseness, asthma, chronic sinusitis, or other otorhinolaryngologic diseases. Sinusitis patients have pain similar to the elderly and people with arthritis A new analysis led by researchers at Georgetown University Medical Center suggests many patients with sinusitis have aches and pains similar in severity to people in their 80s and those with arthritis or depression. Retail medical clinics attract patients who do not have regular health care providers Retail medical clinics located in pharmacies and other stores typically attract insured and uninsured patients who are seeking help for a small group of easy-to-treat illnesses or preventive care and do not otherwise have a regular health care provider, according to a new RAND Corporation study. Innate immune system targets asthma-linked fungus for destruction A new study shows that the innate immune system of humans is capable of killing a fungus linked to airway inflammation, chronic rhinosinusitis and bronchial asthma. More Sinusitis Current Events and Sinusitis News Articles |
|||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||