Details

Autor(en) / Beteiligte

• PREHN, John L
• LANDERS, Carol
• MULLER, George W
• MAN, Hon-Wah
• STIRLING, David I
• TARGAN, Stephan R

Titel

Potent inhibition of cytokine production from intestinal lamina propria T cells by phosphodiesterase-4 inhibitory thalidomide analogues

Ist Teil von

• Journal of clinical immunology, 2001-09, Vol.21 (5), p.357-364

Ort / Verlag

New York, NY: Kluwer/Plenum

Erscheinungsjahr

2001

Quelle

SpringerLINK Contemporary (Konsortium Baden-Württemberg)

Beschreibungen/Notizen

• In Crohn's disease, intestinal lamina propria (LP) T cells overproduce TNF-alpha and IFN-gamma, and clinical and animal studies indicate that this is pathogenic. Thalidomide influences cytokine production by leukocytes, inhibiting macrophage TNF-alpha, and is beneficial in treating Crohn's disease. Chemical analogues have been synthesized that may lack teratogenic and other side effects of thalidomide. We tested three analogues [selective cytokine inhibitory drugs (SelCIDs) A, B, and C, all potent PDE4 inhibitors] for effect on TNF-alpha, IFN-gamma, and IL-10 production by and on proliferation of intestinal LP mononuclear cells after T-cell stimulation and results were compared with those for peripheral blood leukocytes (PBL). While thalidomide itself had little effect, the SelCIDs were potent inhibitors, with relative inhibitory potencies: A> or =B>>C. The LP T cells were less sensitive to inhibition by the SelCIDs than were PBL. Since highly pre-activated PBL were even less sensitive, activation state alone can account for the responsiveness of intestinal LP T cells. Thalidomide analogues could play a role in treating Crohn's disease and other inflammatory disorders.