IL-2 and IL-4 counteract budesonide inhibition of GM-CSF and IL-10, but not of IL-8, IL-12 or TNF-alpha production by human mononuclear blood cells

1 The combination of interleukin-2 (IL-2) and IL-4 reduces the inhibitory e ffects of glucocorticoids on granulocyte-macrophage colony-stimulating fact or (GM-CSF) production, in agreement with the hypothesis that this combinat ion causes glucocorticoid resistance. Whether a general cytokine resistance to glucocorticoids is induced by IL-2 and IL-4 has not been reported. 2 Mononuclear blood cells from healthy individuals were pre-treated with IL -2, IL-4, or IL-2 + IL-4 (31.3-500 U ml(-1)) for 48 h, prior to lipopolysac charide (LPS; 10 ng ml(-1); 20 h) and budesonide addition. Cytokine levels in the supernatants were analysed using specific immunoassays. DNA content was analysed to estimate cell numbers. 3 GM-CSF production was totally inhibited by budesonide at 10(-8) M in vehi cle treated cultures, while IL-IO was inhibited to 33.3 +/- 4.3% of control . IL-2, IL-4, or IL-2 + IL-4 reduced the inhibitory effects of budesonide o n GM-CSF to similar levels (23.7 +/- 6.7, 31.6 +/- 8.5 and 35.1 +/- 4.3% of control, respectively). IL-2, IL-4, or IL-2 + IL-4 also reduced the inhibi tory effects of budesonide on IL-10 production (46.5 +/- 6.6, 55.9 +/- 7.3% , and 68.3 +/- 9.9% of control, respectively). In contrast, IL-8, IL-12 and TNF-alpha production did not become resistant to budesonide. 4 Thus, glucocorticoid resistance induced by IL-2 and IL-4 is not general a t the cytokine production level. While the glucocorticoid sensitivity of GM -CSF and IL-IO production decreased, the sensitivity of IL-8, IL-12 or TNF- alpha production was unchanged. Also, the mixture of IL-2 and IL-4 is not c rucial for induction of glucocorticoid resistance of GM-CSF production.