Elevated cytokine messenger RNA levels in the peripheral blood of patients with rheumatoid arthritis suggest different degrees of myeloid cell activation

Hendrik Schulze-Koops, Laurie S. Davis, Arthur F. Kavanaugh, Peter E. Lipsky

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Objective. To determine whether monocytes in rheumatoid arthritis (RA) are activated to produce proinflammatory cytokines in the peripheral circulation before entering the synovium and whether the pattern of cytokines that is expressed correlates with disease activity. Methods. Cytokine messenger RNA (mRNA) levels were assessed in peripheral blood mononuclear cells (PBMC) from 14 RA patients and 14 healthy controls by semiquantitative reverse transcription-polymerase chain reaction technology. The method employed was sufficiently sensitive to assess cytokine mRNA levels in freshly isolated cells without the necessity of in vitro stimulation. Thus, an estimate of the in vivo state of activation could be obtained. Results. Interleukin-8 (IL-8) mRNA levels were elevated in all 14 RA patients compared with normal controls, whereas 7 of 14 RA patients had elevated levels of mRNA for IL-6 or IL-10. IL-1β mRNA levels were below the normal range in 3 of 14 patients, within normal limits in 4 of 14, and elevated in 7 of 14. Tumor necrosis factor α mRNA levels were within the normal range in 9 of 14 patients and below normal in 5 of 14. There was a statistically significant difference between the mean IL-10 (P < 0.05) and IL-8 (P < 0.001) mRNA levels in RA patients and normal controls. Of note, the 7 patients with elevated IL- 1β mRNA levels also expressed the highest levels of IL-8 mRNA. Whereas a strong correlation between the expression of IL-1β and IL-8 mRNA (P < 0.001) was found, expression of all other mRNA occurred independently of each other. Levels of cyclooxygenase 2 (COX-2) mRNA were also determined to evaluate the status of myeloid cell activation more completely. COX-2 mRNA levels were within the normal range in 4 of 11 patients and below normal in 7 of 11, but did not correlate with the expression of any of the cytokine mRNA. Conclusion. Elevated levels of mRNA for selected cytokines that are predominantly produced by monocytes can be found in the PBMC of many RA patients. The data indicate that myeloid precursor cells become activated to produce cytokines before they enter the synovium, a finding which emphasizes the systemic nature of RA.

Original languageEnglish (US)
Pages (from-to)639-647
Number of pages9
JournalArthritis and Rheumatism
Volume40
Issue number4
DOIs
StatePublished - 1997

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Myeloid Cells
Rheumatoid Arthritis
Cytokines
Messenger RNA
Interleukin-8
Interleukin-1
Reference Values
Synovial Membrane
Cyclooxygenase 2
Interleukin-10
Monocytes
Blood Cells
Reverse Transcription
Interleukin-6

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Elevated cytokine messenger RNA levels in the peripheral blood of patients with rheumatoid arthritis suggest different degrees of myeloid cell activation. / Schulze-Koops, Hendrik; Davis, Laurie S.; Kavanaugh, Arthur F.; Lipsky, Peter E.

In: Arthritis and Rheumatism, Vol. 40, No. 4, 1997, p. 639-647.

Research output: Contribution to journalArticle

Schulze-Koops, Hendrik ; Davis, Laurie S. ; Kavanaugh, Arthur F. ; Lipsky, Peter E. / Elevated cytokine messenger RNA levels in the peripheral blood of patients with rheumatoid arthritis suggest different degrees of myeloid cell activation. In: Arthritis and Rheumatism. 1997 ; Vol. 40, No. 4. pp. 639-647.
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abstract = "Objective. To determine whether monocytes in rheumatoid arthritis (RA) are activated to produce proinflammatory cytokines in the peripheral circulation before entering the synovium and whether the pattern of cytokines that is expressed correlates with disease activity. Methods. Cytokine messenger RNA (mRNA) levels were assessed in peripheral blood mononuclear cells (PBMC) from 14 RA patients and 14 healthy controls by semiquantitative reverse transcription-polymerase chain reaction technology. The method employed was sufficiently sensitive to assess cytokine mRNA levels in freshly isolated cells without the necessity of in vitro stimulation. Thus, an estimate of the in vivo state of activation could be obtained. Results. Interleukin-8 (IL-8) mRNA levels were elevated in all 14 RA patients compared with normal controls, whereas 7 of 14 RA patients had elevated levels of mRNA for IL-6 or IL-10. IL-1β mRNA levels were below the normal range in 3 of 14 patients, within normal limits in 4 of 14, and elevated in 7 of 14. Tumor necrosis factor α mRNA levels were within the normal range in 9 of 14 patients and below normal in 5 of 14. There was a statistically significant difference between the mean IL-10 (P < 0.05) and IL-8 (P < 0.001) mRNA levels in RA patients and normal controls. Of note, the 7 patients with elevated IL- 1β mRNA levels also expressed the highest levels of IL-8 mRNA. Whereas a strong correlation between the expression of IL-1β and IL-8 mRNA (P < 0.001) was found, expression of all other mRNA occurred independently of each other. Levels of cyclooxygenase 2 (COX-2) mRNA were also determined to evaluate the status of myeloid cell activation more completely. COX-2 mRNA levels were within the normal range in 4 of 11 patients and below normal in 7 of 11, but did not correlate with the expression of any of the cytokine mRNA. Conclusion. Elevated levels of mRNA for selected cytokines that are predominantly produced by monocytes can be found in the PBMC of many RA patients. The data indicate that myeloid precursor cells become activated to produce cytokines before they enter the synovium, a finding which emphasizes the systemic nature of RA.",
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N2 - Objective. To determine whether monocytes in rheumatoid arthritis (RA) are activated to produce proinflammatory cytokines in the peripheral circulation before entering the synovium and whether the pattern of cytokines that is expressed correlates with disease activity. Methods. Cytokine messenger RNA (mRNA) levels were assessed in peripheral blood mononuclear cells (PBMC) from 14 RA patients and 14 healthy controls by semiquantitative reverse transcription-polymerase chain reaction technology. The method employed was sufficiently sensitive to assess cytokine mRNA levels in freshly isolated cells without the necessity of in vitro stimulation. Thus, an estimate of the in vivo state of activation could be obtained. Results. Interleukin-8 (IL-8) mRNA levels were elevated in all 14 RA patients compared with normal controls, whereas 7 of 14 RA patients had elevated levels of mRNA for IL-6 or IL-10. IL-1β mRNA levels were below the normal range in 3 of 14 patients, within normal limits in 4 of 14, and elevated in 7 of 14. Tumor necrosis factor α mRNA levels were within the normal range in 9 of 14 patients and below normal in 5 of 14. There was a statistically significant difference between the mean IL-10 (P < 0.05) and IL-8 (P < 0.001) mRNA levels in RA patients and normal controls. Of note, the 7 patients with elevated IL- 1β mRNA levels also expressed the highest levels of IL-8 mRNA. Whereas a strong correlation between the expression of IL-1β and IL-8 mRNA (P < 0.001) was found, expression of all other mRNA occurred independently of each other. Levels of cyclooxygenase 2 (COX-2) mRNA were also determined to evaluate the status of myeloid cell activation more completely. COX-2 mRNA levels were within the normal range in 4 of 11 patients and below normal in 7 of 11, but did not correlate with the expression of any of the cytokine mRNA. Conclusion. Elevated levels of mRNA for selected cytokines that are predominantly produced by monocytes can be found in the PBMC of many RA patients. The data indicate that myeloid precursor cells become activated to produce cytokines before they enter the synovium, a finding which emphasizes the systemic nature of RA.

AB - Objective. To determine whether monocytes in rheumatoid arthritis (RA) are activated to produce proinflammatory cytokines in the peripheral circulation before entering the synovium and whether the pattern of cytokines that is expressed correlates with disease activity. Methods. Cytokine messenger RNA (mRNA) levels were assessed in peripheral blood mononuclear cells (PBMC) from 14 RA patients and 14 healthy controls by semiquantitative reverse transcription-polymerase chain reaction technology. The method employed was sufficiently sensitive to assess cytokine mRNA levels in freshly isolated cells without the necessity of in vitro stimulation. Thus, an estimate of the in vivo state of activation could be obtained. Results. Interleukin-8 (IL-8) mRNA levels were elevated in all 14 RA patients compared with normal controls, whereas 7 of 14 RA patients had elevated levels of mRNA for IL-6 or IL-10. IL-1β mRNA levels were below the normal range in 3 of 14 patients, within normal limits in 4 of 14, and elevated in 7 of 14. Tumor necrosis factor α mRNA levels were within the normal range in 9 of 14 patients and below normal in 5 of 14. There was a statistically significant difference between the mean IL-10 (P < 0.05) and IL-8 (P < 0.001) mRNA levels in RA patients and normal controls. Of note, the 7 patients with elevated IL- 1β mRNA levels also expressed the highest levels of IL-8 mRNA. Whereas a strong correlation between the expression of IL-1β and IL-8 mRNA (P < 0.001) was found, expression of all other mRNA occurred independently of each other. Levels of cyclooxygenase 2 (COX-2) mRNA were also determined to evaluate the status of myeloid cell activation more completely. COX-2 mRNA levels were within the normal range in 4 of 11 patients and below normal in 7 of 11, but did not correlate with the expression of any of the cytokine mRNA. Conclusion. Elevated levels of mRNA for selected cytokines that are predominantly produced by monocytes can be found in the PBMC of many RA patients. The data indicate that myeloid precursor cells become activated to produce cytokines before they enter the synovium, a finding which emphasizes the systemic nature of RA.

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