Antiflammins. Anti-inflammatory activity and effect on human phospholipase A2.
Two anti-inflammatory peptides (antiflammins) corresponding to a high amino acid similarity region between lipocortin I and uteroglobin were tested for their ability to inhibit purified human synovial fluid phospholipase A2 (HSF-PLA2). No inhibitory activity was observed, even at such high concentrations of peptides as 50 microM. When antiflammins were preincubated with the enzyme and/or the substrate, no HSF-PLA2 inhibition was detected. In vivo anti-inflammatory activity of these peptides was evaluated in several experimental models of inflammation induced by carrageenan, croton-oil, oxazolone and Naja naja naja venom phospholipase A2 (PLA2). In contrast to the in vitro results, anti-inflammatory activity was observed in all tests, except when inflammation was induced by snake venom PLA2. Taken together, our results do not support the hypothesis that the in vivo anti-inflammatory effect of antiflammins is directly related to inhibition of PLA2 activity.
Cabré
F
F
Departamento R & D, Laboratorios Menarini S.A., Badalona, Spain.
Moreno
J J
JJ
Carabaza
A
A
Ortega
E
E
Mauleón
D
D
Carganico
G
G
D000818:Animals; D017302:Annexins; D000893:Anti-Inflammatory Agents; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000201:enzymology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology; D051379:Mice; D010179:Pancreas / Q000201:enzymology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D012176:Retinoids / Q000494:pharmacology; D013552:Swine; D013582:Synovial Fluid / Q000187:drug effects / Q000201:enzymology; D014598:Uteroglobin / Q000494:pharmacology*
D017302:Annexins; D000893:Anti-Inflammatory Agents; D002135:Calcium-Binding Proteins; D012176:Retinoids; D014598:Uteroglobin; D010741:Phospholipases A; D054467:Phospholipases A2