Regulation of interleukin-1 receptor antagonist by Th1 and Th2 cytokines.
Airway inflammation is an important aspect of asthma. Recent studies of airway inflammation in asthma have focused attention on cytokines released by T helper lymphocyte type 1 (Th1)- and Th2-like T cells. Interleukin (IL)-1 is also increased in the airways of asthmatics, and it is most likely derived from airway and alveolar macrophages. The effects of Th1 or Th2 cytokines on the release of IL-1 or its specific antagonist, IL-1ra, have not been well studied. We examined the response of THP-1 cells, a myelomonocytic cell line, to stimulation with various Th1 and Th2 cytokines and found that IL-4, IL-10, and IFN-gamma increased IL-1ra mRNA and protein release. The increase in mRNA was not due to an increase in IL-1ra mRNA stability. IL-4 (10 ng/ml) increased IL-1ra release from 9,641 +/- 322 [from cells stimulated with lipopolysaccharide (LPS) alone] to 50,796 +/- 1,917 pg/ml (from cells stimulated with LPS and IL-4). IL-10 (10 ng/ml) caused a similar upregulation of IL-1ra from LPS-stimulated cells: 87,478 +/- 7,808 compared with 8,004 +/- 1,166 pg/ml released from the cells stimulated with LPS alone. Cells stimulated with IFN-gamma (100 U/ml) and LPS released 27,854 +/- 3,626 pg/ml of IL-1ra, compared with 9,069 +/- 236 pg/ml in the presence of LPS alone. In addition, the Th1 cytokine, IFN-gamma, but not the Th2 cytokines, IL-4 and IL-10, upregulated IL-1 beta mRNA and increased the release of IL-1 beta protein. Similar studies were performed using freshly isolated monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Kline
J N
JN
Department of Medicine, University of Iowa College of Medicine, Iowa City, USA.
Fisher
P A
PA
Monick
M M
MM
Hunninghake
G W
GW
D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012795:Sialoglycoproteins / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D007371:Interferon-gamma