Elevated monocytic IL-12 and TNF-α production in Wegener's granulomatosis is normalized by cyclophosphamide and corticosteroid therapy

P. Lamprecht, G. Kumanovics, A. Mueller, Elena Csernok, A. Komócsi, A. Trabandt, W. L. Gross, A. Schnabel

Research output: Contribution to journalArticle

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Abstract

Wegener's granulomatosis (WG) is characterized by a predominance of the type 1 T-helper cell (Th1) response. We have studied monocytic cytokine expression in untreated patients and in patients who did not respond to prior methotrexate or trimethoprim-sulphamethoxazole therapy, i.e. patients with active disease. Intracytoplasmic IL-12 and TNF-α expression was significantly increased in WG compared with healthy controls. IL-8 expression was not increased. Two and 12 weeks of daily standard oral cyclophosphamide and corticosteroid (CYC + GC) treatment induced a stable remission of the disease. Elevated IL-12 and TNF-α expression of monocytes was normalized. The active metabolite of CYC was shown to down-regulate IL-12 mRNA in vitro. Monocytic cytokines, especially IL-12, may have a role in the early determination and skewing of the immunoregulatory response towards a Th1 profile. It appears that CYC + GC exerts its effect by normalizing the Th1-driving cytokine pattern, and CYC may maintain this mode of action. Normalization of the skewed cytokine pattern may be a prerequisite and an indicator of inducing a remission in WG.

Original languageEnglish
Pages (from-to)181-186
Number of pages6
JournalClinical and Experimental Immunology
Volume128
Issue number1
DOIs
Publication statusPublished - 2002

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Granulomatosis with Polyangiitis
Interleukin-12
Cyclophosphamide
Adrenal Cortex Hormones
Cytokines
Sulfamethoxazole
Th1 Cells
Trimethoprim
Therapeutics
Interleukin-8
Methotrexate
Monocytes
Down-Regulation
Messenger RNA

Keywords

  • Cyclophosphamide
  • IL-12
  • TNF-α
  • Wegener's granulomatosis

ASJC Scopus subject areas

  • Immunology

Cite this

Elevated monocytic IL-12 and TNF-α production in Wegener's granulomatosis is normalized by cyclophosphamide and corticosteroid therapy. / Lamprecht, P.; Kumanovics, G.; Mueller, A.; Csernok, Elena; Komócsi, A.; Trabandt, A.; Gross, W. L.; Schnabel, A.

In: Clinical and Experimental Immunology, Vol. 128, No. 1, 2002, p. 181-186.

Research output: Contribution to journalArticle

Lamprecht, P. ; Kumanovics, G. ; Mueller, A. ; Csernok, Elena ; Komócsi, A. ; Trabandt, A. ; Gross, W. L. ; Schnabel, A. / Elevated monocytic IL-12 and TNF-α production in Wegener's granulomatosis is normalized by cyclophosphamide and corticosteroid therapy. In: Clinical and Experimental Immunology. 2002 ; Vol. 128, No. 1. pp. 181-186.
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