Abstract
We have compared the immunosuppressive effect of delta HOP and glucocorticoids on lymphocyte proliferation and IL-1 secretion. The new synthetic steroid only inhibited proliferation of phytohaemagglutinin (PHA)-stimulated human lymphocyte at high concentrations and the effect did not persist after washing out the steroid. In contrast, glucocorticoids produced the classical dose-response inhibition and the effect persisted when they were removed from the cultured medium. Although both steroids decreased IL-1 secretion from human monocytes stimulated with lipopolysaccharide (LPS), they exert the same effect through a different mechanism. The experiments we report suggest that the decrease of IL-1 synthesis produced by delta HOP could be caused by inhibition of LPS phagocytosis. These results support our hypothesis that delta HOP exerts its immunosuppressive and anti-inflammatory effect by a non-genomic mechanism.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allison A. C., Lee S. W. The mode of action of anti-rheumatic drugs. 1. Anti-inflammatory and immunosuppressive effects of glucocorticoids. Prog Drug Res. 1989;33:63–81. doi: 10.1007/978-3-0348-9146-2_3. [DOI] [PubMed] [Google Scholar]
- Becker J., Grasso R. J. Suppression of phagocytosis by dexamethasone in macrophage cultures: inability of arachidonic acid, indomethacin, and nordihydroguaiaretic acid to reverse the inhibitory response mediated by a steroid-inducible factor. Int J Immunopharmacol. 1985;7(6):839–847. doi: 10.1016/0192-0561(85)90046-3. [DOI] [PubMed] [Google Scholar]
- Duval D., Durant S., Homo-Delarche F. Non-genomic effects of steroids. Interactions of steroid molecules with membrane structures and functions. Biochim Biophys Acta. 1983 Aug 11;737(3-4):409–442. doi: 10.1016/0304-4157(83)90008-4. [DOI] [PubMed] [Google Scholar]
- González M. D., Rondinone C. M., Burton G., Lantos C. P., Roldán A. Mechanism of the inhibitory effect of 11 beta-hydroxypregna-1, 4-diene-3, 20-dione (delta HOP) at high concentrations in RNA synthesis. Acta Physiol Pharmacol Latinoam. 1986;36(3):303–312. [PubMed] [Google Scholar]
- Knudsen P. J., Dinarello C. A., Strom T. B. Glucocorticoids inhibit transcriptional and post-transcriptional expression of interleukin 1 in U937 cells. J Immunol. 1987 Dec 15;139(12):4129–4134. [PubMed] [Google Scholar]
- Mogensen C. E. The glomerular permeability determined by dextran clearance using Sephadex gel filtration. Scand J Clin Lab Invest. 1968;21(1):77–82. doi: 10.3109/00365516809076979. [DOI] [PubMed] [Google Scholar]
- Roldán A., Burton G., Castillo M. B., Damasco M. C., Lantos C. P. Inhibition of thymocyte RNA synthesis by natural adrenal steroids and their 1,4-diene analogs. Structure-activity correlations using 13C-n.m.r. spectroscopy. J Steroid Biochem. 1981 Dec;15:467–472. doi: 10.1016/0022-4731(81)90316-2. [DOI] [PubMed] [Google Scholar]
- Rondinone C. M., Roldán A. Effect of 11 beta OH pregna-1,4-diene-3,20-dione (delta HOP) on thymocyte plasma membranes. Acta Physiol Pharmacol Latinoam. 1990;40(3):357–364. [PubMed] [Google Scholar]
- Rondinone C. M., Schillaci R., Lantos C. P., Roldán A. Appearance and persistence of 11 beta-hydroxypregna-1,4-diene-3,20-dione (delta HOP) effect "in vivo". Acta Physiol Pharmacol Latinoam. 1989;39(2):181–188. [PubMed] [Google Scholar]
- Warner S. J., Savage N., Mitchell D. Characteristics of lipopolysaccharide interaction with human peripheral-blood monocytes. Biochem J. 1985 Dec 1;232(2):379–383. doi: 10.1042/bj2320379. [DOI] [PMC free article] [PubMed] [Google Scholar]
