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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

Larsson, Susanne (author)
Lund University,Lunds universitet,Lungmedicin, allergologi och palliativ medicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Respiratory Medicine, Allergology, and Palliative Medicine,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
Löfdahl, Claes-Göran (author)
Lund University,Lunds universitet,Lungmedicin, allergologi och palliativ medicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Respiratory Medicine, Allergology, and Palliative Medicine,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
Linden, M (author)
 (creator_code:org_t)
2009-01-29
1999
English.
In: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 127:4, s. 980-986
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 1. The combination of interleukin-2 (IL-2) and IL-4 reduces the inhibitory effects of glucocorticoids on granulocyte-macrophage colony-stimulating factor (GM-CSF) production, in agreement with the hypothesis that this combination 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 lipopolysaccharide (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 vehicle treated cultures, while IL-10 was inhibited to 33.4+/-4.3% of control. IL-2, IL-4, or IL-2 + IL-4 reduced the inhibitory effects of budesonide on 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 inhibitory 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 at the cytokine production level. While the glucocorticoid sensitivity of GM-CSF and IL-10 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 crucial for induction of glucocorticoid resistance of GM-CSF production.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Keyword

GM-CSF
IL-4
Glucocorticoid resistance
budesonide
IL-2
IL-8
IL-10
IL-12
TNF-a
mononuclear blood cells

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art (subject category)
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