We have located links that may give you full text access.
Journal Article
Research Support, Non-U.S. Gov't
Persistence of bronchopulmonary hyper-reactivity and eosinophilic lung inflammation after anti-IL-5 or -IL-13 treatment in allergic BALB/c and IL-4Ralpha knockout mice.
Clinical and Experimental Allergy 2003 January
BACKGROUND: Antigen-induced bronchopulmonary hyper-reactivity (BHR) is generally associated with eosinophilia. It involves cytokines produced by Th2 lymphocytes, including IL-4, IL-5 and IL-13, which are implicated in IgE production, eosinophil differentiation and attraction, and related events relevant to allergic inflammation, whose mechanisms remain unclear.
OBJECTIVE: To investigate the mechanisms by which Th2 cytokines mediate eosinophilia and subsequent BHR using ovalbumin (OVA)-immunized and OVA-challenged IL-4Ralpha-/- and IL-4-/- mice, which fail to transduce and/or to produce IL-4 and IgE as compared with wild type (WT) mice, and specific neutralizing antibodies.
METHODS: On days 0 and 7, mice were immunized subcutaneously (s.c.) with OVA. At day 14, anti-IL-5 or anti-IL-13 antibodies were administered intranasally and/or intravenously before allergenic challenge. Different functional and cellular parameters were studied in vivo and cytokine production was followed with a newly described ex vivo procedure using lung explants.
RESULTS: IL-4Ralpha-/- and IL-4-/- mice developed BHR and pulmonary eosinophilia, even though eosinophil recruitment to the bronchoalveolar liquid lavage (BALF) was reduced. In vivo, IL-4-/- and IL-4Ralpha-/- mice produced, respectively, no or reduced amounts of IL-5 in the BALF/serum as compared with WT mice, whereas no IL-13 in the BALF was detected. By contrast, ex vivo, surviving lung explants from WT and IL-4-/- or IL-4Ralpha-/- mice produced IL-13 and large amounts of IL-5. The neutralization of IL-5 in vivo (BALF and serum) and ex vivo (from lung explant) in IL-4Ralpha-/- and WT mice failed to suppress BHR and lung eosinophilia, and to modify IL-13 production ex vivo. In addition, neutralization of IL-13 in vivo from lung explant also failed to abrogate BHR and lung eosinophilia, whereas IL-5 was unchanged.
CONCLUSION: Antigen-induced BHR can develop independently from IL-4, IL-5 or IL-13 and from the IL-4alpha receptor chain, suggesting a possible novel IL-4, IL-5 and IL-13-independent pathway for the development of BHR in allergic BALB/c mice. The failure of IL-5 or IL-13 antibodies to prevent BHR in IL-4Ralpha-/- mice suggests that neither is indispensable for BHR but does not exclude a role for lung tissue eosinophilia.
OBJECTIVE: To investigate the mechanisms by which Th2 cytokines mediate eosinophilia and subsequent BHR using ovalbumin (OVA)-immunized and OVA-challenged IL-4Ralpha-/- and IL-4-/- mice, which fail to transduce and/or to produce IL-4 and IgE as compared with wild type (WT) mice, and specific neutralizing antibodies.
METHODS: On days 0 and 7, mice were immunized subcutaneously (s.c.) with OVA. At day 14, anti-IL-5 or anti-IL-13 antibodies were administered intranasally and/or intravenously before allergenic challenge. Different functional and cellular parameters were studied in vivo and cytokine production was followed with a newly described ex vivo procedure using lung explants.
RESULTS: IL-4Ralpha-/- and IL-4-/- mice developed BHR and pulmonary eosinophilia, even though eosinophil recruitment to the bronchoalveolar liquid lavage (BALF) was reduced. In vivo, IL-4-/- and IL-4Ralpha-/- mice produced, respectively, no or reduced amounts of IL-5 in the BALF/serum as compared with WT mice, whereas no IL-13 in the BALF was detected. By contrast, ex vivo, surviving lung explants from WT and IL-4-/- or IL-4Ralpha-/- mice produced IL-13 and large amounts of IL-5. The neutralization of IL-5 in vivo (BALF and serum) and ex vivo (from lung explant) in IL-4Ralpha-/- and WT mice failed to suppress BHR and lung eosinophilia, and to modify IL-13 production ex vivo. In addition, neutralization of IL-13 in vivo from lung explant also failed to abrogate BHR and lung eosinophilia, whereas IL-5 was unchanged.
CONCLUSION: Antigen-induced BHR can develop independently from IL-4, IL-5 or IL-13 and from the IL-4alpha receptor chain, suggesting a possible novel IL-4, IL-5 and IL-13-independent pathway for the development of BHR in allergic BALB/c mice. The failure of IL-5 or IL-13 antibodies to prevent BHR in IL-4Ralpha-/- mice suggests that neither is indispensable for BHR but does not exclude a role for lung tissue eosinophilia.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
Perioperative echocardiographic strain analysis: what anesthesiologists should know.Canadian Journal of Anaesthesia 2024 April 11
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app