title: Human recombinant lipocortin 1 has acute local anti-inflammatory properties in the rat paw edema test.
abstract: Human recombinant lipocortin 1 has been tested for anti-inflammatory activity in a conventional model of acute inflammation. Microgram amounts of the protein, locally administered, inhibited edema of the rat paw when induced by subplantar injections of carrageenin: the ED50 was 10-20 micrograms per paw, and inhibition (maximum of 60-70%) was not dependent upon an intact adrenal cortex. Doses of lipocortin that produced approximately 50% inhibition in the carrageenin test were inactive against edema elicited by bradykinin, serotonin, platelet-activating factor-acether, or dextran, whereas edema caused by Naja mocambique venom phospholipase A2 was strongly inhibited by lipocortin. The protein inhibited edema when rats were pretreated with agents that depleted mast-cell amines, kininogen, or polymorphonuclear leukocytes prior to initiation of the carrageenin edema but had no inhibitory action when rats were pretreated with the dual cyclooxygenase/lipoxygenase inhibitor BW 755C. These results demonstrate that human recombinant lipocortin has potent local anti-inflammatory activity, probably through selectively interfering with eicosanoid generation. Lipocortin is relatively ineffective against edema caused by mast-cell degranulation or kinins, except when degranulation is caused by phospholipase A2.
authors: Pharmacology Group, School of Pharmacy and Pharmacology, University of Bath, Claverton Down, United Kingdom.
authors: G
authors: G
authors: Cirino
authors: S H
authors: SH
authors: Peers
authors: R J
authors: RJ
authors: Flower
authors: J L
authors: JL
authors: Browning
authors: R B
authors: RB
authors: Pepinsky
mesh_terms: D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000315:Adrenalectomy; D000818:Animals; D017302:Annexins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001920:Bradykinin; D002351:Carrageenan; D003907:Dexamethasone / Q000494:pharmacology; D003911:Dextrans; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006023:Glycoproteins / Q000627:therapeutic use*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D010740:Phospholipases / Q000037:antagonists & inhibitors; D010741:Phospholipases A; D054467:Phospholipases A2; D010972:Platelet Activating Factor; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology*; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D017302:Annexins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003911:Dextrans; D006023:Glycoproteins; D010972:Platelet Activating Factor; D011720:Pyrazoles; D011994:Recombinant Proteins; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D003907:Dexamethasone; D002351:Carrageenan; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D001920:Bradykinin; D007213:Indomethacin; D008727:Methotrexate