T-cell derived lymphokines as regulators of chronic inflammation: Potential targets for immunomodulation?

Jorg J. Goronzy, Kenneth N. Gold, Cornelia M. Weyand

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

In recent years, compelling evidence has accumulated that inflammation results from a cascade of events that are orchestrated by cytokines. Cytokines are products of nonimmune and immune cells which regulate the recruitment, differentiation, and proliferation of inflammatory cells. Although there is redundancy in cytokine production and function, major pathways of cytokines have been identified. Besides macrophages, T cells represent important sources of pro- and anti-inflammatory cytokines. In support of a critical regulatory role of T cells in inflammation, two T cell subtypes characterized by different cytokine profiles have been described. TH1 cells produce interleukin-2 (IL-2) and interferon-γ (IFN-γ) and are prone to interact with macrophages. TH2 cells are producers of IL-4, IL-5, and IL-10 and are capable of supporting B cells and eosinophils. Here, we are providing evidence that different human inflammatory diseases are characterized by distinct in situ cytokine patterns. Giant cell vasculitis represents a typical TH1-like disease, whereas TH2 helper cells appear to be more important in rheumatoid arthritis. Given the association of different diseases with cytokine profiles, the question arises how the microenvironment influences cytokine pattern and thus disease and whether mediators produced at the site of inflammation could serve as therapeutic targets to modulate the cytokine cascade. Prostaglandin E2 (PGE2) is an important inflammatory mediator. We have examined the influence of PGE2 and the PGE analog misoprostol on T-cell function and T-cell cytokine production. Here, we describe that IL-2 and IFN-γ production are sensitive to PGE2 and misoprostol, whereas IL-4 and IL-5 are unaffected. Thus, in the presence of PGE2, TH0 cells acquire a TH2-like function, whereas TH1-like aspects are suppressed. We suggest that PGE2 and misoprostol might represent useful modulators of the cytokine network.

Original languageEnglish (US)
Pages (from-to)109-114
Number of pages6
JournalAmerican journal of therapeutics
Volume3
Issue number2
DOIs
StatePublished - Feb 1996

Keywords

  • giant cell arteritis
  • immunoregulation
  • lymphokines
  • misoprostol
  • prostaglandin E
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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