Inhibition profiles of picumast and ketotifen on the in vitro release of prostanoids, slow-reacting substance of anaphylaxis, histamine and enzyme from human leukocytes and rat alveolar macrophages.

The inhibitory potency of the antiallergic compounds picumast (PIC; Boehringer Mannheim) and ketotifen (K; Sandoz) on the release of 3 preformed and 3 newly generated inflammatory mediators was estimated as an indicator for their antiallergic activity. Peripheral human leukocytes (HL) or rat alveolar macrophages (RAM) were stimulated by opsonized zymosan (C3-Z) and/or anti-IgE antibody, following preincubation times with PIC and K. SRS-A was measured with the help of a guinea pig ileum bioassay, PGE2 and TxB2 by RIA (NEN), histamine (H) by an automated fluorimetric procedure, tryptic proteinase (P) by a colorimetric test employing Tos-Gly-Pro-Arg-pNA (Chromozym TH; Boehringer Mannheim) as chromogenic substrate and beta-glucuronidase (beta-G) by a colorimetric test (Sigma). PIC (IC30: 2 X 10(-5) mol/l) was 100 times more potent than K as inhibitor of the anti-IgE-induced release of H and P and also 5 times more potent as inhibitor of SRS-A-formation/release in/from HL. In contrast, on RAM, K (IC30: 7 X 10(-6) mol/l) had a 3 times greater potency as inhibitor of the C3-Z-induced SRS-A formation and suppressed PGE2 release (4 X 10(-5)-2 X 10(-4) mol/l), whereas PIC (2 X 10(-5) mol/l) potentiated PGE2 release remarkably. TxB2 release from RAM was inhibited nearly equipotently by PIC and K. beta-G release was strongly potentiated by K (greater than or equal to 8 X 10(-6) mol/l), but weakly inhibited by PIC (2 X 10(-5) mol/l). PIC (greater than or equal to 4 X 10(-5) mol/l) also increased the beta-G release and in the same manner the anti-IgE- or C3-Z-induced release of other 'preformed' mediators like H and P from HL.(ABSTRACT TRUNCATED AT 250 WORDS)