Therapy using progenitor cells is thought to be of great interest in the future for a variety of diseases including immune-mediated diseases.
Bone marrow stromal cells (mesenchymal stem cells) are thought to “sense” their immune milieu and respond to restore balance. Wow. As the authors of a new article in PNAS comment, “is it possible to imagine a drug doing this?” Nemeth et al. (PNAS 2010 107 (12) 5652-5657; published ahead of print March 15, 2010, doi:10.1073/pnas.0910720107) present results adding to evidence that BMSCs act homeostatically regardless of the direction of immune imbalance.
Nemeth et al. begin with the known inflammation-suppressive effect of BMSC in graft/host disease in humans. This effect is thought to go in the direction of balancing Th1 inflammation toward Th2. The authors decided to look at the effects of BMSCs in a mouse model of allergic asthma to see if BMSCs could re-equilibrate aTh2 environment toward Th1/Th2 balance.
They tested this idea in mice with ragweed-induced asthma, administering syngeneic BMSCs intravenously at the time of challenge. There was virtually global suppression of all asthma-related Th2 inflammatory changes, including a decrease in serum IgE and IgG. Furthermore, the authors demonstrate that BMSCs were recruited specifically to the lung in the mice with asthma.
Looking for possible mechanisms, Nemeth et al. find that up-regulated TGF-β expression by the BMSCs is largely responsible for the anti-inflammatory effects and that this is IL-4R/STAT-6 dependent. The increased TGF-β also positively impacts T-reg numbers in the lung tissue.
Nemeth et al. note that during testing to compare BMSC response from allogeneic and syngeneic sources, they used syngeneic fibroblasts as a control and discover that the fibroblasts had beneficial effects, though the effects were milder.
Is this study going to change the paradigm for the understanding of the treatment of asthma or will it be another experimental study which has little effect in humans with asthma?
Have a comment? Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.
Friday, March 26, 2010
Monday, March 15, 2010
British allergy society issues guidelines for investigating anesthesia-related anaphylaxis
The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) has published guidelines and algorithms for the systematic investigation of anaphylaxis that occurs during general anesthesia. Identifying the allergen is equally as important as identifying the safe alternatives for the patient. Ewan et al. (Clin Exp Allergy 2010 Jan;40(1):15-31.) pressed the importance of these recommendations for accumulating data on anesthetic drugs because there is no supporting data for most drugs used in general anesthesia and it is impossible to do graded challenges with many anesthetic drugs. Additionally, they recommended that the investigation be conducted at a dedicated drug allergy center, to capitalize on the expertise and volume managed at these centers.
The guidelines begin with the obligations of the anesthetist and the allergist, with the anesthetist being responsible for initiating the investigation. Anesthetist responsibilities start post-resuscitation with serum tryptase levels immediately, 1-2 hours, and >24 hours after recovery. They also inform the patient and refer them to the drug allergist. The allergist then follows up with patients and medical documentation to begin the process of identifying most likely causes of anaphylaxis [and distinguishing them from other complications of general anesthesia] and initiating skin prick testing, intradermal testing, and/or challenge. Detailed recommendations for and reliability of technical aspects of the investigation, such as skin prick and cross-reactivity testing, are also covered by Ewan et al.
The authors noted that the most common reaction was to neuromuscular blocking agents [NMBA], though there is an increase in anaphylaxis cases to latex and antibiotics administered peri-anesthetically. They reported that allergic reactions to local anesthetics are extremely rare and that there are no reports of reaction to inhaled anesthesia.
Have a comment? Tell us what you think by posting your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.
The guidelines begin with the obligations of the anesthetist and the allergist, with the anesthetist being responsible for initiating the investigation. Anesthetist responsibilities start post-resuscitation with serum tryptase levels immediately, 1-2 hours, and >24 hours after recovery. They also inform the patient and refer them to the drug allergist. The allergist then follows up with patients and medical documentation to begin the process of identifying most likely causes of anaphylaxis [and distinguishing them from other complications of general anesthesia] and initiating skin prick testing, intradermal testing, and/or challenge. Detailed recommendations for and reliability of technical aspects of the investigation, such as skin prick and cross-reactivity testing, are also covered by Ewan et al.
The authors noted that the most common reaction was to neuromuscular blocking agents [NMBA], though there is an increase in anaphylaxis cases to latex and antibiotics administered peri-anesthetically. They reported that allergic reactions to local anesthetics are extremely rare and that there are no reports of reaction to inhaled anesthesia.
Have a comment? Tell us what you think by posting your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.
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