Anti-inflammatory steroids downregulate gene expression and production of both TH, and THJ cytokines: In vitro-in vivo correlates

R. Ghnwamy, J. K. Smith, K. Hall, S. Srikanth, D. Béais, S. K. Huang, R. Mukkamala, D. S. Chi

Research output: Contribution to journalArticle

Abstract

Anti-inflammatory steroids (AIS) work by modulating gene expression, especially of proinflammatory cytokines secreted by lymphocytes and other inflammatory cells. Based on their secretion of cytokines, T helper cells have been classified into two groups: TH, cells secrete IL2, IFN y and TNF β, while TH2 cells secrete IL-4, 5, 6, 10 and 13. To determine whether steroids have a propensity to inhibit either type, we studied the effects of dexamethasone ([DX]; i-0.0001 uM) on TH,a cytokine gene expression and protein production in peripheral blood mononuclears activated with PHA. We also studied the effects of prednisone (PR) on serum levels and production of TH1/2 cytokines in a patient with Sjogren's syndrome and lymphocytic interstitial pneumonitis. Cytokine gene expression (IL-1RA, IL-2, 4, 5, 6, 8, 13, TNF a, GMCSF and IFN y) was assessed by reverse-transcription polymerase chain reaction (RT-PCR) and quantitative, competitive PCR (cPCR), cytokine production by ELISA, proliferation by [3H]thymidine incorporation and T cell phenotypes by flow cytometry. DX induced a dose dependant suppression of T cell proliferative responses to PHA except at low concentrations (10 ' to W°M) where DX enhanced proliferation. DX (1 M) obliterated expression of transcripts for IL-4 and 5 (3 out of 3;3/3) and IFN y (2/3). The effects of DX in inhibiting IL-5 gene expression was confirmed by cPCR. DX induced a dose-dependant inhibition of IL-5 and IFN y production. In vivo, PR diminished serum levels of both IL-5 and IFN y, and production of these proteins from PHA-activated PBMC's. In summary, AIS non-selectively inhibit production of both TH, and TH2 cytokines. This may explain the pronounced anti-inflammatory action of these drugs and their propensity to serious immunosupression.

Original languageEnglish
JournalJournal of Investigative Medicine
Volume44
Issue number3
Publication statusPublished - Jan 1 1996
Externally publishedYes

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Gene expression
Anti-Inflammatory Agents
Interleukin-5
Dexamethasone
Down-Regulation
Steroids
Cytokines
Gene Expression
Interleukin-4
T-cells
Prednisone
Polymerase Chain Reaction
Interleukin-2
T-Lymphocytes
Lymphocytes
Flow cytometry
Polymerase chain reaction
Sjogren's Syndrome
Interstitial Lung Diseases
Transcription

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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Anti-inflammatory steroids downregulate gene expression and production of both TH, and THJ cytokines : In vitro-in vivo correlates. / Ghnwamy, R.; Smith, J. K.; Hall, K.; Srikanth, S.; Béais, D.; Huang, S. K.; Mukkamala, R.; Chi, D. S.

In: Journal of Investigative Medicine, Vol. 44, No. 3, 01.01.1996.

Research output: Contribution to journalArticle

Ghnwamy, R. ; Smith, J. K. ; Hall, K. ; Srikanth, S. ; Béais, D. ; Huang, S. K. ; Mukkamala, R. ; Chi, D. S. / Anti-inflammatory steroids downregulate gene expression and production of both TH, and THJ cytokines : In vitro-in vivo correlates. In: Journal of Investigative Medicine. 1996 ; Vol. 44, No. 3.
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abstract = "Anti-inflammatory steroids (AIS) work by modulating gene expression, especially of proinflammatory cytokines secreted by lymphocytes and other inflammatory cells. Based on their secretion of cytokines, T helper cells have been classified into two groups: TH, cells secrete IL2, IFN y and TNF β, while TH2 cells secrete IL-4, 5, 6, 10 and 13. To determine whether steroids have a propensity to inhibit either type, we studied the effects of dexamethasone ([DX]; i-0.0001 uM) on TH,a cytokine gene expression and protein production in peripheral blood mononuclears activated with PHA. We also studied the effects of prednisone (PR) on serum levels and production of TH1/2 cytokines in a patient with Sjogren's syndrome and lymphocytic interstitial pneumonitis. Cytokine gene expression (IL-1RA, IL-2, 4, 5, 6, 8, 13, TNF a, GMCSF and IFN y) was assessed by reverse-transcription polymerase chain reaction (RT-PCR) and quantitative, competitive PCR (cPCR), cytokine production by ELISA, proliferation by [3H]thymidine incorporation and T cell phenotypes by flow cytometry. DX induced a dose dependant suppression of T cell proliferative responses to PHA except at low concentrations (10 ' to W°M) where DX enhanced proliferation. DX (1 M) obliterated expression of transcripts for IL-4 and 5 (3 out of 3;3/3) and IFN y (2/3). The effects of DX in inhibiting IL-5 gene expression was confirmed by cPCR. DX induced a dose-dependant inhibition of IL-5 and IFN y production. In vivo, PR diminished serum levels of both IL-5 and IFN y, and production of these proteins from PHA-activated PBMC's. In summary, AIS non-selectively inhibit production of both TH, and TH2 cytokines. This may explain the pronounced anti-inflammatory action of these drugs and their propensity to serious immunosupression.",
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AU - Srikanth, S.

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