Comparison of antiinflammatory and antiallergic drugs in the melittin- and D49 PLA2-induced mouse paw edema models.
Melittin (MLT) (10 micrograms/paw) and D49 (0.4 micrograms/paw) were injected into the hind paw of male CD-1 mice and elicited 70-80% of maximal paw edema responses at 60 and 30 min after injection, respectively. D49 paw edema was significantly inhibited by anti-histamine/serotonin agents, a PAF antagonist, a PLA2 inhibitor, and some but not all 5-LO and CO inhibitors, indicating that this edema is produced by several classes of inflammatory mediators with mast cell degranulation apparently playing a major role. In contrast, MLT paw edema was not inhibited effectively using the same pharmacological agents except theophylline, suggesting it was elicited via a different sequence of inflammatory events. In summary, D49 and MLT paw edema models were found to be ineffective models to identify experimental PLA2 compounds in our laboratory.
Hartman
D A
DA
Department of Experimental Therapeutics Wyeth-Ayerst Research, Princeton, NJ 08543-8000.
Tomchek
L A
LA
Lugay
J R
JR
Lewin
A C
AC
Chau
T T
TT
Carlson
R P
RP
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003594:Cytoplasmic Granules / Q000187:drug effects; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005528:Foot; D006633:Histamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D008555:Melitten; D051379:Mice; D010741:Phospholipases A; D054467:Phospholipases A2
D000893:Anti-Inflammatory Agents; D006633:Histamine Antagonists; D008555:Melitten; D010741:Phospholipases A; D054467:Phospholipases A2