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Control of T-cell responses by the combination of low dose steroids with beta2-agonists
Abstracts S37
trations of FP (10-12-10-11M), and provided greater inhibition as compared to FP alone in control group. Combinatory treatment revealed more efficient GCRalpha translocation within 1h (p<0.01 as compared to 10-12M FP alone). However addition of salmeterol to low doses of FP did not provide any additional proliferation inhibition in asthma group. FP 10-12M/salmeterol 10-7M significantly inhibited TNFalpha and IFNgamma production (p<0.05) (TNFalpha - 68.1 ± 10.8% inhibition, 62.6 ± 4.5%; IFNgamma 77.1 ± 6.1%, 68.0 ± 10.3% in control and asthma groups, respectively), but failed to inhibit Th2 cytokine (IL-5, IL-13) production by allergic asthmatics. Addition of PDE4 inhibitor, rolipram (10-6M), to FP/salmeterol combination enhanced inhibition of T-cell proliferation in asthma group. CONCLUSIONS: Beta2-agonists in combination with low doses of steroids can be beneficial for suppression of PBMC proliferation and cytokine production from healthy individuals, whereas suppression of inflammation in allergic asthmatics requires addition of phosphodiesterase inhibitor. Funding: NIH
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Control of T-Cell Responses by the Combination of Low Dose Steroids With Beta2-Agonists
A. Dunlap, E. Goleva, D. Y. M. Leung; Department of Pediatrics, National Jewish Medical & Research Center, Denver, CO. RATIONALE: Combination treatment of asthma with fluticasone propionate (FP), and long-acting beta2-agonist, salmeterol xinafoate, provides greater asthma control than increasing doses of steroids. Whether beta2agonists can be beneficial not only for bronchodilation, but for suppression of inflammation in asthma is not defined. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy controls and allergic asthmatics were stimulated with 2.5 µg/ml PHA in presence of FP (10-12-10-9M) ± salmeterol (10-12-10-7M) for 72h. The FP response was assessed by inhibition of T-cell proliferation, cytokine production and glucocorticoid receptor alpha (GCRalpha) translocation. RESULTS: Both groups showed similar degrees of inhibition of PHA induced T-cell proliferation by FP (IC50=10-9M). Addition of salmeterol (10-10-10-7M) facilitated proliferation inhibition with much lower concen-
SATURDAY
J ALLERGY CLIN IMMUNOL VOLUME 113, NUMBER 2
trations of FP (10-12-10-11M), and provided greater inhibition as compared to FP alone in control group. Combinatory treatment revealed more efficient GCRalpha translocation within 1h (p<0.01 as compared to 10-12M FP alone). However addition of salmeterol to low doses of FP did not provide any additional proliferation inhibition in asthma group. FP 10-12M/salmeterol 10-7M significantly inhibited TNFalpha and IFNgamma production (p<0.05) (TNFalpha - 68.1 ± 10.8% inhibition, 62.6 ± 4.5%; IFNgamma 77.1 ± 6.1%, 68.0 ± 10.3% in control and asthma groups, respectively), but failed to inhibit Th2 cytokine (IL-5, IL-13) production by allergic asthmatics. Addition of PDE4 inhibitor, rolipram (10-6M), to FP/salmeterol combination enhanced inhibition of T-cell proliferation in asthma group. CONCLUSIONS: Beta2-agonists in combination with low doses of steroids can be beneficial for suppression of PBMC proliferation and cytokine production from healthy individuals, whereas suppression of inflammation in allergic asthmatics requires addition of phosphodiesterase inhibitor. Funding: NIH
49
Control of T-Cell Responses by the Combination of Low Dose Steroids With Beta2-Agonists
A. Dunlap, E. Goleva, D. Y. M. Leung; Department of Pediatrics, National Jewish Medical & Research Center, Denver, CO. RATIONALE: Combination treatment of asthma with fluticasone propionate (FP), and long-acting beta2-agonist, salmeterol xinafoate, provides greater asthma control than increasing doses of steroids. Whether beta2agonists can be beneficial not only for bronchodilation, but for suppression of inflammation in asthma is not defined. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy controls and allergic asthmatics were stimulated with 2.5 µg/ml PHA in presence of FP (10-12-10-9M) ± salmeterol (10-12-10-7M) for 72h. The FP response was assessed by inhibition of T-cell proliferation, cytokine production and glucocorticoid receptor alpha (GCRalpha) translocation. RESULTS: Both groups showed similar degrees of inhibition of PHA induced T-cell proliferation by FP (IC50=10-9M). Addition of salmeterol (10-10-10-7M) facilitated proliferation inhibition with much lower concen-
SATURDAY
J ALLERGY CLIN IMMUNOL VOLUME 113, NUMBER 2