TABLE 5

Inhibition of CD3-induced proliferation and cytokine production in purified human CD4⁺ lymphocytes by ciclesonide, des-CIC, the respective 2′S-epimers BYK20427 and BYK20433, and by budesonide

Highly purified human CD4⁺ lymphocytes were stimulated with a combination of a CD3 mAb and a CD28 mAb in the presence or absence of seven concentrations of steroids ranging from 10⁻⁶ to 10⁻¹² M. After 72 h, the incorporation of [³H]thymidine and the synthesis of cytokines were measured. Efficacy of inhibition was 80% for proliferation, and for synthesis of cytokines 90% (IL-2), 70 % (IL4), 90 % (IL-5), 90% (IFN-γ). IC₅₀ values denote half-maximal inhibition and were determined using nonlinear regression. In general, six to eight concentration-inhibition curves were evaluated to calculate an average IC₅₀. For inhibition of IL-4 synthesis, only three to four concentration-inhibition curves were evaluated as some cell preparations produced very low titers of IL-4.