Neutrophil-activating peptide 1/interleukin 8 mRNA expression and protein secretion by human monocytes: effect of cyclosporin A

Cytokine. 1991 Jul;3(4):322-6. doi: 10.1016/1043-4666(91)90500-d.

Abstract

Neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8) is a recently described cytokine with potent chemotactic activity for human neutrophil granulocytes (PMN) and T cells. In psoriasis, a chronic hyperproliferative and inflammatory skin disorder, PMN and T cells are found as prominent cells in the inflammatory infiltrate of the lesions; however, monocytes were shown to be the first cells invading a newly formed plaque. NAP-1/IL-8 was found to be present in high amounts in the skin and in scale material of psoriatic patients. Psoriasis responds well to systemic treatment with cyclosporin A (CsA), an immunosuppressive peptide. Therefore, we addressed the question of whether the clinical improvement of psoriatic patients during CsA therapy may be due to an inhibition of NAP-1/IL-8 production and secretion from monocytes. Purified human monocytes were stimulated by lipopolysaccharide in the presence or absence of various concentrations of CsA. Production of NAP-1/IL-8 was determined as expression of specific mRNA by fluorescent in situ hybridization. Secreted peptide was measured by bioassay (PMN chemotaxis) and enzyme-linked immunosorbent assay (ELISA) using specific monoclonal antibodies. The results show that CsA neither inhibited mRNA expression for NAP-1/IL-8 nor secretion of the peptide. These findings support the hypothesis that the pharmacological effect of CsA may be restricted to the inhibition of T-cell activation and proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclosporins / pharmacology*
  • Gene Expression / drug effects
  • Humans
  • In Vitro Techniques
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / metabolism
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism
  • Psoriasis / drug therapy
  • Psoriasis / immunology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*

Substances

  • Cyclosporins
  • Interleukin-8
  • RNA, Messenger