BACKGROUND: Lymphocytes play a central role in the pathophysiology of asthma. Corticosteroids have a limited effect in severe asthma and we hypothesise that lymphocytes play a central role in corticosteroid insensitivity. We investigated the effects of corticosteroids on cytokine production from lung lymphocytes obtained from patients with moderate severe asthma (MSA) compared to mild asthma (MA) and healthy non-smokers (HNS). METHODS: Bronchoalveolar lavage (BAL) cells obtained by bronchoscopy from patients with MSA and MA (n = 11 and n = 14 respectively) and HNS (n = 7) were stimulated with CD2/3/28 beads to activate the lymphocytes, in the presence or absence of dexamethasone (0.01-1 μM). Supernatants were assayed for IL-2, IFNγ, IL-17, IL-13 and IL-10 production. RESULTS: Dexamethasone caused variable inhibition of cytokines; 1 μM inhibited IL-10 and IL-17 by 50% or lower, while inhibition > 50% was observed for IL-2, IL-13 and IFNγ. The effect of dexamethasone on IL-13 production was reduced in MSA. CONCLUSION: These findings suggest that the production of specific lymphocyte derived cytokines is poorly suppressed by corticosteroids in MSA, which may be responsible for persistent airway inflammation in these patients
BACKGROUND: Lymphocytes play a central role in the pathophysiology of asthma. Corticosteroids have a limited effect in severe asthma and we hypothesise that lymphocytes play a central role in corticosteroid insensitivity. We investigated the effects of corticosteroids on cytokine production from lung lymphocytes obtained from patients with moderate severe asthma (MSA) compared to mild asthma (MA) and healthy non-smokers (HNS). METHODS: Bronchoalveolar lavage (BAL) cells obtained by bronchoscopy from patients with MSA and MA (n = 11 and n = 14 respectively) and HNS (n = 7) were stimulated with CD2/3/28 beads to activate the lymphocytes, in the presence or absence of dexamethasone (0.01-1 μM). Supernatants were assayed for IL-2, IFNγ, IL-17, IL-13 and IL-10 production. RESULTS:Dexamethasone caused variable inhibition of cytokines; 1 μM inhibited IL-10 and IL-17 by 50% or lower, while inhibition > 50% was observed for IL-2, IL-13 and IFNγ. The effect of dexamethasone on IL-13 production was reduced in MSA. CONCLUSION: These findings suggest that the production of specific lymphocyte derived cytokines is poorly suppressed by corticosteroids in MSA, which may be responsible for persistent airway inflammation in these patients
Authors: Michael C Peters; Sheena Kerr; Eleanor M Dunican; Prescott G Woodruff; Merritt L Fajt; Bruce D Levy; Elliot Israel; Brenda R Phillips; David T Mauger; Suzy A Comhair; Serpil C Erzurum; Mats W Johansson; Nizar N Jarjour; Andrea M Coverstone; Mario Castro; Annette T Hastie; Eugene R Bleecker; Sally E Wenzel; John V Fahy Journal: J Allergy Clin Immunol Date: 2018-03-07 Impact factor: 10.793
Authors: Julia A Wisniewski; Lyndsey M Muehling; Jacob D Eccles; Brian J Capaldo; Rachana Agrawal; Debbie-Ann Shirley; James T Patrie; Lisa J Workman; Alexander J Schuyler; Monica G Lawrence; W Gerald Teague; Judith A Woodfolk Journal: J Allergy Clin Immunol Date: 2017-09-20 Impact factor: 10.793
Authors: Thomas Southworth; Jonathan Plumb; Vandana Gupta; James Pearson; Isabel Ramis; Martin D Lehner; Montserrat Miralpeix; Dave Singh Journal: Respir Res Date: 2016-10-04