AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 1 92-L98, Copyright © 1995 by American Physiological Society
Regulation of interleukin-1 receptor antagonist by Th1 and Th2 cytokines
J. N. Kline, P. A. Fisher, M. M. Monick and G. W. Hunninghake
Department of Medicine, University of Iowa College of Medicine, Iowa City, USA.
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)
