TY - JOUR
T1 - The effects of corticosteroids on cytokine production from asthma lung lymphocytes.
AU - Kaur, Manminder
AU - Reynolds, Sophie
AU - Smyth, Lucy J
AU - Simpson, Karen
AU - Hall, Simon
AU - Singh, Dave
PY - 2014/12
Y1 - 2014/12
N2 - 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
AB - 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
U2 - 10.1016/j.intimp.2014.10.008
DO - 10.1016/j.intimp.2014.10.008
M3 - Article
C2 - 25466265
SN - 1878-1705
VL - 23
JO - International immunopharmacology
JF - International immunopharmacology
IS - 2
ER -