The inhibitory effects of topically active glucocorticoids on IL-4, IL-5, and interferon-gamma production by cultured primary CD4+ T cells.
This study was conducted to directly compare the in vitro efficacy and potency of several glucocorticoids in inhibiting T-cell cytokine production. The glucocorticoids tested were fluticasone propionate, budesonide, triamcinolone acetonide, and beclomethasone dipropionate, which are currently inhaled therapies for the treatment of allergic airway disease. Also used were betamethasone phosphate and the newly developed mometasone furorate. With a novel cell culture system, purified peripheral blood CD4+ T cells from normal donors were stimulated with immobilized anti-CD3 and soluble anti-CD28 monoclonal antibodies to induce high levels of IL-4, IL-5, and interferon-gamma. By cell sorting, it was found that the IL-5 produced originated from memory cells, whereas both memory and naive cells produced interferon-gamma. Mometasone and fluticasone inhibited IL-5 and IL-4 similarly (mometasone IL-5 inhibitory concentration of 50% = 0.27 +/- 0.1 nmol/L and IL-4 = 0.19 +/- 0.08 nmol/L). For both cytokines, the results indicate that mometasone and fluticasone were more potent than beclomethasone, triamcinolone, budesonide, and betamethasone. Of clinical importance is the finding that all steroids demonstrated less efficacy versus interferon-gamma than IL-4 and IL-5. Glucocorticoid reduction of Th2 cytokines with lesser effects on interferon-gamma would serve to reverse the exaggerated Th2 response that contributes to pathophysiology observed in allergic disease. Therefore the use of topically active glucocorticoids with low systemic bioactivity for the treatment of allergic inflammation may be particularly effective in modulating the cytokine activity that is an important component of the allergic response.
Umland
S P
SP
Schering-Plough Research Institute, Kenilworth, N.J. 07033, USA.
Nahrebne
D K
DK
Razac
S
S
Beavis
A
A
Pennline
K J
KJ
Egan
R W
RW
Billah
M M
MM
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D003864:Depression, Chemical; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000378:metabolism; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000378:metabolism; D013268:Stimulation, Chemical; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism
D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma