Kinetics of Cytokine Production in Experimental Systemic Lupus Erythematosus Involvement of T Helper Cell 1/T Helper Cell 2-Type Cytokines in Disease

Raphael Segal, Bonnie L. Bermas, Molly Dayan, Francis Kalush, Gene M. Shearer, Edna Mozes

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Abstract

We followed cytokine production from induction through disease progression in a murine model of experimental systemic lupus erythematosus (SLE). SLE was induced by immunization with the human monoclonal anti-DNA Ab that bears the common Id designated 16/6 Id. BALB/c and C3H.SW mice that are susceptible to SLE induction and C57BL/6 mice that are resistant were immunized with the 16/6 Id. Cytokine production was tested periodically for 7 mo. Increased production of IL-2 and IFN-γ, the Th1-type cytokines, was detected in BALB/c and C3H.SW mice 2 to 4 mo following immunization. IL-4 and IL-10, the Th2-type cytokines predominated later in disease course, and peaked 5 mo following disease induction. At this stage the Th1 type cytokines dropped to levels below those observed in controls. IL-4 production also dropped rapidly to very low levels, while IL-10 production decreased but remained above control levels. The ratio of IgG2a/IgG1 of DNA and 16/6 Id-specific Abs peaked at 2 mo following disease induction and decreased later, in concordance with the higher production of Th2-type cytokines. Thus, the development of experimental SLE in mice involves two stages: increased production of Th1-type, followed by increased induction of Th2-type cytokines. High levels of the proinflammatory cytokines, TNF-α and IL-1, were maintained throughout disease course. No significant changes were detected in the cytokine profile of C57BL/6 immunocytes following immunization with the 16/6 Id, supporting the possible role of the cytokine network in SLE.

Original languageEnglish (US)
Pages (from-to)3009-3016
Number of pages8
JournalJournal of Immunology
Volume158
Issue number6
StatePublished - Mar 15 1997

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Th2 Cells
Th1 Cells
Systemic Lupus Erythematosus
Cytokines
Immunization
Interleukin-4
Interleukin-10
DNA
Interleukin-1
Inbred C57BL Mouse
Interleukin-2
Disease Progression
Theoretical Models
Immunoglobulin G

ASJC Scopus subject areas

  • Immunology

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Kinetics of Cytokine Production in Experimental Systemic Lupus Erythematosus Involvement of T Helper Cell 1/T Helper Cell 2-Type Cytokines in Disease. / Segal, Raphael; Bermas, Bonnie L.; Dayan, Molly; Kalush, Francis; Shearer, Gene M.; Mozes, Edna.

In: Journal of Immunology, Vol. 158, No. 6, 15.03.1997, p. 3009-3016.

Research output: Contribution to journalArticle

Segal, Raphael ; Bermas, Bonnie L. ; Dayan, Molly ; Kalush, Francis ; Shearer, Gene M. ; Mozes, Edna. / Kinetics of Cytokine Production in Experimental Systemic Lupus Erythematosus Involvement of T Helper Cell 1/T Helper Cell 2-Type Cytokines in Disease. In: Journal of Immunology. 1997 ; Vol. 158, No. 6. pp. 3009-3016.
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abstract = "We followed cytokine production from induction through disease progression in a murine model of experimental systemic lupus erythematosus (SLE). SLE was induced by immunization with the human monoclonal anti-DNA Ab that bears the common Id designated 16/6 Id. BALB/c and C3H.SW mice that are susceptible to SLE induction and C57BL/6 mice that are resistant were immunized with the 16/6 Id. Cytokine production was tested periodically for 7 mo. Increased production of IL-2 and IFN-γ, the Th1-type cytokines, was detected in BALB/c and C3H.SW mice 2 to 4 mo following immunization. IL-4 and IL-10, the Th2-type cytokines predominated later in disease course, and peaked 5 mo following disease induction. At this stage the Th1 type cytokines dropped to levels below those observed in controls. IL-4 production also dropped rapidly to very low levels, while IL-10 production decreased but remained above control levels. The ratio of IgG2a/IgG1 of DNA and 16/6 Id-specific Abs peaked at 2 mo following disease induction and decreased later, in concordance with the higher production of Th2-type cytokines. Thus, the development of experimental SLE in mice involves two stages: increased production of Th1-type, followed by increased induction of Th2-type cytokines. High levels of the proinflammatory cytokines, TNF-α and IL-1, were maintained throughout disease course. No significant changes were detected in the cytokine profile of C57BL/6 immunocytes following immunization with the 16/6 Id, supporting the possible role of the cytokine network in SLE.",
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