Platelet-activating factor (PAF) in allergic diseases: inhibitory effects of anti-allergic drugs, ketotifen and three kampo medicines on PAF production.
Platelet-activating factor (PAF) is considered an important mediator in allergic and inflammatory reactions. To further investigate the role of PAF in allergic diseases, we examined the in vitro and ex vivo effect of anti-allergic drugs on PAF production by human neutrophils. Ketotifen and three Kampo medicines, which are widely used in the treatment of allergic diseases in Japan, inhibited PAF production by normal human neutrophils dose-dependently, whereas disodium chromoglycate (DSCG) and tranilast did not have any inhibitory effect. Ketotifen also suppressed ex vivo PAF production by neutrophils from healthy subjects. PAF production decreased from 40.5 +/- 5.0 units to 21.6 +/- 4.7 units after oral administration of 2 mg of ketotifen per day for one week. We also measured the concentration of lysoPAF in serum from patients with Japanese cedar pollinosis during the pollen season and followed the effect of ketotifen on lysoPAF levels in the serum from these patients. We found that the concentration of lysoPAF, a precursor and degradation product of PAF, in patients with cedar pollinosis (87.8 +/- 8.7 units) was significantly higher than in healthy subjects (54.7 +/- 7.7 units). After two weeks, lysoPAF levels decreased significantly (82.6 units to 41.3 units) only in the group treated with nasal aerosol and ketotifen. These results suggest that PAF may play a role in allergic diseases and that the clinical effects of anti-allergic drugs may at least partially be due to their anti-PAF action.
Nakamura
T
T
Department of Internal Medicine, School of Medicine, University of Tokyo, Japan.
Kuriyama
M
M
Ishihara
K
K
Matsumura
Y
Y
Miyamoto
T
T
D000328:Adult; D004205:Cromolyn Sodium / Q000494:pharmacology / Q000627:therapeutic use*; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000188:drug therapy*; D007665:Ketotifen / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008516:Medicine, Chinese Traditional; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D011058:Pollen; D012016:Reference Values; D062367:ortho-Aminobenzoates / Q000494:pharmacology / Q000627:therapeutic use*
D006634:Histamine H1 Antagonists; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D062367:ortho-Aminobenzoates; C012293:tranilast; D004205:Cromolyn Sodium; D007665:Ketotifen