BACKGROUND: Psoriasis is a T-helper (Th)1 cytokine-mediated chronic skin disease and interleukin (IL)-12 has been shown to play a major role in the development of Th1 responses. OBJECTIVES: To elucidate the role of IL-12 in the pathogenesis of psoriasis and to study the effect of ciclosporin A (CsA) on Th1 deviation of this disease. PATIENTS/ METHODS: We investigated IL-12 production by stimulated monocytes from patients with psoriasis who were treated with or without CsA. Monocytes were stimulated with interferon-gamma plus lipopolysaccharide (LPS) or Staphylococcus aureus Cowan strain I (SAC). The amount of IL-12 p70 produced by stimulated monocytes was evaluated by enzyme-linked immunosorbent assay. RESULTS: Compared with those from normal controls, LPS- but not SAC-stimulated monocytes from patients with psoriasis produced significantly higher amounts of IL-12. Interestingly, LPS-stimulated monocytes from patients with psoriasis treated with CsA produced significantly decreased amounts of IL-12 compared with those patients not treated with CsA. CONCLUSIONS: Our results suggest that IL-12 production by monocytes may have a critical role in the pathogenesis of psoriasis, and that the therapeutic effect of CsA on psoriasis may be achieved by correcting the deviation of the Th1/Th2 balance.
BACKGROUND:Psoriasis is a T-helper (Th)1 cytokine-mediated chronic skin disease and interleukin (IL)-12 has been shown to play a major role in the development of Th1 responses. OBJECTIVES: To elucidate the role of IL-12 in the pathogenesis of psoriasis and to study the effect of ciclosporin A (CsA) on Th1 deviation of this disease. PATIENTS/ METHODS: We investigated IL-12 production by stimulated monocytes from patients with psoriasis who were treated with or without CsA. Monocytes were stimulated with interferon-gamma plus lipopolysaccharide (LPS) or Staphylococcus aureus Cowan strain I (SAC). The amount of IL-12 p70 produced by stimulated monocytes was evaluated by enzyme-linked immunosorbent assay. RESULTS: Compared with those from normal controls, LPS- but not SAC-stimulated monocytes from patients with psoriasis produced significantly higher amounts of IL-12. Interestingly, LPS-stimulated monocytes from patients with psoriasis treated with CsA produced significantly decreased amounts of IL-12 compared with those patients not treated with CsA. CONCLUSIONS: Our results suggest that IL-12 production by monocytes may have a critical role in the pathogenesis of psoriasis, and that the therapeutic effect of CsA on psoriasis may be achieved by correcting the deviation of the Th1/Th2 balance.
Authors: Chunjian Liu; James Lin; Ryan Moslin; John S Tokarski; Jodi Muckelbauer; ChiehYing Chang; Jeffrey Tredup; Dianlin Xie; Hyunsoo Park; Peng Li; Dauh-Rurng Wu; Joann Strnad; Adriana Zupa-Fernandez; Lihong Cheng; Charu Chaudhry; Jing Chen; Cliff Chen; Huadong Sun; Paul Elzinga; Celia D'arienzo; Kathleen Gillooly; Tracy L Taylor; Kim W McIntyre; Luisa Salter-Cid; Louis J Lombardo; Percy H Carter; Nelly Aranibar; James R Burke; David S Weinstein Journal: ACS Med Chem Lett Date: 2019-02-21 Impact factor: 4.345