[Effect of salazosulfapyridine and its metabolites on immunocompetent cells].
Long-term administration of SASP does offer clinical benefit and has a demonstrable disease modifying effect in rheumatoid arthritis, though its mode of action remains obscure. We have studied the in vitro effects of SASP and its metabolites, that is SP, ASA, AcSP and AcASA, on the blast-formation of lymphocytes, the cytotoxic activity of NK cell, the phagocytosis and H2O2 production of monocyte and the fMLP-induced chemotaxis and superoxide anions production of PMNs. We have obtained the following results: (1) the blast-formation of lymphocytes by PHA and Protein A was significantly inhibited by SASP, but not by the metabolites; (2) the cytotoxic activity of the NK cell was inhibited by SP and AcSP, but not by SASP, ASA and AcASA; (3) on monocyte, SP, AcSP and AcASA inhibited phagocytosis, and all of drugs had no effect on the production of H2O2; (4) on PMNs, SASP, SP and ASA significantly inhibited fMLP-induced chemotaxis, and SASP and all of its metabolites significantly inhibited a release of superoxide anions by stimulation of fMLP and PMA; (5) SASP and ASA scavenged superoxide radical at the concentration comparable to clinical doses. In vivo, the above effects may be exhibited in proportion to each blood concentrations of drugs. In particular, it appears that SASP, SP and AcSP play an important role in the therapeutic efficacy in rheumatoid arthritis.
Ishibashi
T
T
Hara
A
A
Tsuboi
I
I
Muraoka
T
T
Shibata
H
H
Tsunosue
R
R
Shichijo
S
S
Yokoyama
M
M
D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D012460:Sulfasalazine / Q000494:pharmacology*
D012460:Sulfasalazine