Treatment of peripheral blood mononuclear cells with 8-methoxypsoralen plus ultraviolet A radiation induces a shift in cytokine expression from a Th1 to a Th2 response.

Abstract

Treatment with 8-methoxypsoralen plus ultraviolet A radiation and extracorporeal photochemotherapy (photopheresis) are widely used for the treatment of psoriasis and other inflammatory skin diseases, graft-versus-host disease, and mycosis fungoides. As the ratio of Th1 and Th2 cells appears to be critical for pathogenesis and progression of these disorders the effect of psoralen plus ultraviolet A on Th1 and Th2 cytokine production by CD4+ lymphocytes was investigated. Human peripheral blood lymphocytes were incubated in the presence of anti-CD3, rh-IL2, and rh-IL4 for 48 h. After subsequent stimulation with rh-IL2 and rh-IL4 for 72 h cells were treated with 8-methoxypsoralen (100, 500, 1000 ng per ml) plus ultraviolet A (2 J per cm2) and incubated for a further period of 5 h in the presence of ionomycine, phorbol-12-myristate acetate and monensin. Fluorescence-activated cell sorter analysis revealed a significant reduction of interleukin-2- and interferon-gamma-producing CD4+ cells upon psoralen plus ultraviolet A treatment depending on the concentration of 8-methoxypsoralen. In contrast, interleukin-4-producing CD4+ cells were increased, indicating a shift from Th1 to a Th2 cell cytokine profile upon psoralen plus ultraviolet A treatment. These results indicate that 8-methoxypsoralen photochemotherapy of lymphocytes is able to modulate their Th1/Th2 distribution. Inhibition of Th1 cytokine expression by psoralen plus ultraviolet A might help to explain its beneficial effects in the treatment of Th1 dominated skin diseases.

• Authors: G Klosner, F Trautinger, R Knobler, P Neuner
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 116 Issue 3 Pg. 459-62 (Mar 2001) ISSN: 0022-202X [Print] United States
• PMID: 11231322 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Interleukin-2
• Interleukin-4
• Interferon-gamma
• Methoxsalen

Topics

• Cells, Cultured
• Cytokines (blood)
• Humans
• Interferon-gamma (biosynthesis)
• Interleukin-2 (biosynthesis)
• Interleukin-4 (biosynthesis)
• Methoxsalen (pharmacology)
• Monocytes (drug effects, radiation effects)
• Osmolar Concentration
• Th1 Cells (metabolism)
• Th2 Cells (metabolism)
• Ultraviolet Rays