Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indometacin farnesil (Indo-F) is a prodrug of indomethacin designed to reduce the occurrence of side-effects by esterification of the carboxyl group on indomethacin with farnesol. We have examined the pharmacological kinetics and action of Indo-F in peripheral blood mononuclear cells (PBMNC) and polymorphonuclear leukocytes (PBPNL) from patients with rheumatoid arthritis (RA). PBMNC and PBPNL were obtained from 31 RA patients. Indo-F was incubated with PBMNC or PBPNL in the presence or absence of granulocyte-macrophage colony stimulating factor (GM-CSF) (100 pg/ml) for 3 approximately 7 days, after which the concentrations of Indo-F and indomethacin in the culture supernatants or in the cytoplasm extracts were measured with HPLC. The levels of Indo-F in the culture supernatants were significantly decreased in the presence of PBMNC or PBPNL from either normal individuals or RA patients. Indo-F was found to be taken up by PBMNC as well as by PBPNL from RA patients. Conversion of Indo-F into indomethacin was significantly enhanced by GMCSF in the presence of PBMNC, but not PBPNL. The results indicate that Indo-F is taken up by peripheral blood leukocytes from RA patients. Moreover, the data suggest that monocyte-lineage cells might play an important role in the conversion of Indo-F into indomethacin since GM-CSF markedly facilitated the conversion in the presence of PBMNC, but not PBPNL.
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PMID:Interaction of indometacin farnesil, a new nonsteroidal antiinflammatory drug with peripheral blood mononuclear cells from patients with rheumatoid arthritis. 870 90

Indometacin farnesil (INF) is a prodrug of indomethacin (IND) designed to reduce the occurrence of side-effects by esterification of the carboxyl group on IND with farnesol. Previous studies have shown that INF has the characteristics of disease-modifying anti-rheumatic drug (DMARD) in that it has a component of slow-acting effect in treatment of rheumatoid arthritis (RA), in which abnormal B cell functions are considered to be involved. The current studies therefore examined the effects of INF on human B cells. Ig production was induced from highly purified B cells obtained from healthy donors by stimulation with Staphylococcus aureus Cowan I (SA) plus IL-2. T cell proliferation and IFN-gamma production were induced from highly purified T cells by stimulation with immobilized mAb to CD3. At pharmacologically attainable concentrations, INF, but not IND, suppressed the production of IgM and IgG of B cells, whereas neither suppressed the T cell proliferation and IFN-gamma production. The inhibition of Ig production by INF is not due to its IND structure, but is most likely due to its farnesil component, since farnesol alone comparably suppressed the Ig production. INF and farnesol did not suppress the expression of early activation markers, including CD98, CD25, and CD71, on SA-stimulated B cells, but appeared to inhibit the maturation of B cells following the initial activation. These results indicate that INF preferentially suppresses the human B cell functions. Thus, the data suggest that INF may have more beneficial effects than IND in treatment of RA.
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PMID:Inhibition of human B cell activation by a novel nonsteroidal anti-inflammatory drug, indometacin famesil. 1059 81