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- Title
Estrogens interfere with leflunomide modulation of cytokine production by human activated monocytes.
- Authors
Montagna, Paola; Soldano, Stefano; Brizzolara, Renata; Villaggio, Barbara; Triolo, Pierfranco; Clerico, Paolo; Meroni, Marianna; Sulli, Alberto; Seriolo, Bruno; Molfetta, Luigi; Cutolo, Maurizio
- Abstract
Rheumatoid arthritis (RA) prevalence is greater in females than in males, supporting estrogens as modulators of immune response. Leflunomide (LEF) is employed in the RA treatment. We studied the combinatory effects of LEF active metabolite A77 1726 (LEF-M) and 17beta-estradiol (E2) on inflammatory cytokine production by cultured macrophages obtained from activated human monocytes (THP-1 cells). Macrophages were cultured with LEF-M alone and in combination with E2. IL-6, TNF-α, and TGF-β were evaluated by immunocytochemistry (ICC), Western blot (WB), and reverse transcriptase-polymerase chain reaction (RT-PCR). ICC, as well as WB and RT-PCR, showed that LEF-M, in respect to untreated cells, significantly downregulated the cytokine production (IL-6 P < 0.01, TNF-α P < 0.001, TGF-β P < 0.01). On the contrary, E2 increased the cytokine production, a result that was significantly reversed when LEF-M was subsequently added (IL-6, TNF-α, TGF-β P < 0.001 vs. E2). E2 seems to contrast the LEF-M activity. These results might support a more efficient therapeutical effect of LEF in male with respect to female RA patients.
- Subjects
RHEUMATOID arthritis; LEFLUNOMIDE; NONSTEROIDAL anti-inflammatory agents; OXAZOLES; IMMUNOSUPPRESSIVE agents
- Publication
Annals of the New York Academy of Sciences, 2010, Vol 1193, Issue 1, p30
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1111/j.1749-6632.2009.05298.x