Efficacy of soluble IL-4 receptor for the treatment of adults with asthma

Borish, Larry; Nelson, Harold S.; Corren, Jonathan; Bensch, George; Busse, William W.; Whitmore, James B.; Agosti, Jan M.

doi:10.1067/mai.2001.115624

Cited by 381 publications

(175 citation statements)

References 39 publications

Supporting

Mentioning

167

Contrasting

Unclassified

Order By: Relevance

“…Thus, vaccine and therapeutic development should aim to target both B and T cell immunity for optimal efficacy. Early B cell-specific IL-4Rα blocking may be a possible therapy for type 1 diseases, as recently demonstrated in IL-4-driven allergy (56) and others (57,58), and reciprocally, early IFN-γ/IFN-γ receptor and IL-12 blocking may be beneficial for type 2 diseases. However, further research is required to determine if such a therapy might be applicable for all cutaneous Leishmania given the strain and model specificity reported for IL-4 in this disease.…”

Section: Discussionmentioning

confidence: 99%

IL-4–producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases

Hurdayal

Ndlovu

Revaz-Breton

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Interleukin-4 (IL-4)-induced T helper (Th) 2 cells promote susceptibility to the protozoan parasite Leishmania major, while conferring immunity to the intestinal trematode Schistosoma mansoni. Here, we report that abrogation of IL-4 receptor alpha (IL-4Rα) signaling on B cells in BALB/c mice (mb1 cre IL-4Rα -/lox ) transformed nonhealer BALB/c to a healer phenotype with an early type 1 and dramatically reduced type 2 immune response and an absence of ulceration and necrosis during cutaneous leishmaniasis. From adoptive reconstitution and mixed bone-marrow chimera studies in B cell-deficient (μMT) mice, we reveal a central role for B cellderived IL-4 and IL-4Rα in the optimal induction of the susceptible type 2 phenotype to L. major infection. We further demonstrate that the absence of IL-4Rα signaling on B cells exacerbated S. mansoniinduced mortality and pathology in BALB/c mice, due to a diminished type 2 immune response. In both disease models, IL-4Rα-responsive B cells displayed increased IL-4 production as early as day 1 after infection. Together, these results demonstrate that IL-4-producing and IL-4Rα-responsive B cells are critical in regulating and assisting early T helper dichotomy toward Th2 responses, which are detrimental in cutaneous leishmaniasis but beneficial in acute schistosomiasis.IL-4R alpha | B cells | leishmaniasis | schistosomiasis | mouse

show abstract

Section: Discussionmentioning

confidence: 99%

IL-4–producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases

Hurdayal

Ndlovu

Revaz-Breton

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In asthmatics, numbers of CD4 T cells and Th2 cytokines are elevated in bronchoalveolar lavage (BAL) specimens after allergen challenge, suggesting that Th2 responses drive chronic allergic lung inflammation (34). Despite this, therapies targeting either CD4ϩ cells or Th2 cytokines, including IL-4 and IL-5, have not been as successful as anticipated (3,11,24). Although this may be due to many factors such as patient population, dose, duration, and outcome measures, it is also possible that our understanding of how CD4 T cells or other CD4ϩ cells contribute to chronic asthma pathogenesis, including airway remodeling, is inadequate.…”

Section: Cd4 T Cells; Asthma; Th2mentioning

confidence: 99%

CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling

Doherty¹,

Soroosh²,

Broide³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Borish et al (22,23) reported the results of treating asthmatic patients by soluble recombinant humanIL-4 receptor.…”

Section: Application Of Il-4 and -5 Analogues To Newtreatments For Asmentioning

confidence: 99%

“…once a week and were followed for 84 days (23). During the IL-4R inhalation period, concomitant therapy, other than nonantihistamine decongestants and beta-stimulants, was not allowed.…”

Section: Application Of Il-4 and -5 Analogues To Newtreatments For Asmentioning

confidence: 99%

Allergic Bronchial Asthma: Airway Inflammation and Hyperresponsiveness

et al. 2003

View full text Add to dashboard Cite

The international consensus report on diagnosis and treatment of asthma was published in 1992 (Clin ExpAllergy 22: 1-72). According to the report, asthma is a chronic inflammatory disorder of the airways in which many cells play a role, including mast cells and eosinophils.Airway inflammation causes various symptoms of asthma which are usually associated with widespread but variable airflow obstruction and causes an associated increase in airway responsiveness to a variety of stimuli. The definition of asthma, provided in this report, is an epoch-making revision of the conventional recognition of asthma based on respiratory physiology and does not contradict the empirical knowledge that asthma responds well to steroid therapy. One reason, which led airway inflammation to be understood as a major factor in the pathophysiology of asthma is the technological advance and the widespread use of bronchoscopes. The use of bronchoscopyas a research tool has markedly improved the understanding of the pathology of asthma. It became also possible to link biopsy findings to autopsy findings in patients who died of asthma. However, it is relatively difficult to repeat a biopsy of the airway mucosal membranes in individual asthmatic patients. Here, animal models of asthma play a significant role. Findings from animal models can provide a clue for the development of new anti-asthmatic drugs. This paper will deal with the paradigm of allergic asthma and focus on recent topics of interleukin (IL)-4 and IL-5, which seem to play a central role in allergic asthma. The causative relationship between airway inflammation and hyperresponsiveness will be discussed. (Internal Medicine 42: 636-643, 2003)

show abstract

Efficacy of soluble IL-4 receptor for the treatment of adults with asthma

Cited by 381 publications

References 39 publications

IL-4–producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases

IL-4–producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases

CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling

Allergic Bronchial Asthma: Airway Inflammation and Hyperresponsiveness

Contact Info

Product

Resources

About