Augmentation of glucocorticoid action on human monocytes by interleukin-4.
For their anti-inflammatory effects, glucocorticoids act, at least in part, by suppression of the production of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alpha) and prostaglandin E2 (PGE2) by activated monocytes/macrophages. Interleukin-4 (IL-4) also suppresses similar parameters of monocyte activation in vitro. However, contrasting effects of IL-4 and dexamethasone (Dex) on monocyte tissue-type plasminogen activator (t-PA) production suggest that these agents may operate by different pathways. We have now demonstrated that levels of IL-4 as low as 0.05-0.1 U/ml (0.6-1.2 x 10(-11)M) can augment the actions of Dex (5 x 10(-9)M) as an inhibitor of the production of monocyte pro-inflammatory mediators. These in vitro results suggest the possible supplementation of steroid therapy with low amounts of IL-4 (or an agonist) permitting the use of less steroid with concomitant reduction in steroid-associated side-effects. IL-4 can also suppress the increased release of IL-1 beta and TNF alpha by monocytes incubated with indomethacin, a non-steroidal anti-inflammatory drug.
Hart
P H
PH
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Whitty
G A
GA
Burgess
D R
DR
Croatto
M
M
Hamilton
J A
JA
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology*; D008262:Macrophage Activation / Q000502:physiology; D009000:Monocytes / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005938:Glucocorticoids; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D011451:Prostaglandin-Endoperoxide Synthases; D010959:Tissue Plasminogen Activator; D015232:Dinoprostone