Drug activity "in vitro" and "in vivo" on leucocyte chemotaxis.
Drug influences on polymorphonuclear leucocytes (PMN) and particularly on PMN migration was investigated. PMN chemotaxis and random migration were assessed in vitro, after drug incubation in vitro and/or administration in vivo. An inhibiting effect on directed migration induced both by fMLP and C5a was demonstrated with some anti-inflammatory drugs whereas random migration was unaffected. The effect was dose-related and linked to drug chemical structure and to physiopathological state of the cells. Similar results may be obtained after administration in vivo. However some examples show that metabolism can inactivate the pharmacological effect of chemical substances and that the route of administration is of prime importance. The activity of new pathological compounds on PMN migration might need to be studied both in vitro and in vivo. In vitro experiments might be performed as a first step of the study. However only in vivo experiments are really representative of potential therapeutical use. Thus we conclude that both experimental series may be performed to appreciate drug interaction with PMN functions during clinical assays.
Roch-Arveiller
M
M
Département de Pharmacologie, Hôpital Cochin, UA 595 CNRS, Paris, France.
Pham-Huy
D
D
Muntaner
O
O
Maman
L
L
Giroud
J P
JP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D001183:Arthus Reaction / Q000473:pathology; D055598:Chemical Phenomena; D002621:Chemistry; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003182:Complement C5 / Q000502:physiology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010998:Pleurisy / Q000473:pathology; D051381:Rats; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003182:Complement C5; D009240:N-Formylmethionine Leucyl-Phenylalanine