Regulation of interleukin 1 receptor antagonist (il-1ra) by th1 and
th2 cytokines.
Kline, Joel N., Paul A. Fisher, Martha M. Monick, and Gary W.
Hunninghake.
Department of Medicine, University of Iowa College of Medicine and
Veterans Affairs Medical Center, Iowa City, IA 52242
APStracts 2:0029L, 1995.
Airways inflammation is an important aspect of asthma. Recent studies
of airway inflammation in asthma have focused attention on cytokines
released by Th1- and Th2-like T-cells. 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 pg/ml (from cells stimulated with 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 pg/ml 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. These data suggest
that the Th2 cytokines, IL-4 and IL-10, may cause an overall
reduction of IL-1 activity. The findings may be relevant to the
inflammatory response of asthma.
Received 6 May 1994; accepted in final form 17 February 1995.
APS Manuscript Number L130-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 7 March 1995.