Chemiluminescence (CL) in blood samples reflects leukocyte activation (LA) during anaphylactoid reactions in dogs.

Inflammation is accompanied by leukocyte activation (LA). We describe a simple ex vivo technique for studying LA that might help to find new LA inhibitors for the treatment of pathologic events related to LA. Arterial and venous blood samples obtained from six permanently catheterized beagle dogs -60, 0, +15 min and +23 h after i.v. challenge with C 48/80, and also blood samples from six normal beagles, were minimally diluted 1:2.5 with buffer. Total leukocyte counts (LC), and luminol amplified CL, induced by opsonized zymosan (C3-Z), were estimated. Blood samples from dogs elicited CL responses of almost 1/10 the magnitude of erythrocyte-free human leukocytes, whereas blood samples from rats reacted three orders of magnitude less. Obviously quenching of CL by accompanying erythrocytes in blood samples from dogs is not important, for CL correlated almost linearly with the CL in differently diluted samples. In arterial, but not in venous samples from catheterized dogs, absolute CL and LC, both were significantly depressed (p less than or equal to 0.05) 15 min after C 48/80 challenge. CL/10(6) leukocytes was augmented twofold. All leukocyte deviations returned to pre-values 23 h post-challenge.

Nimesulide, indomethacin, BW 755 C, phenidon, mepacrin and nedocromil inhibit the activation of human and rat leucocytes.

This study confirms the strong inhibition of therapeutic concentrations of the antiinflammatory agent nimesulide (NI) on the chemiluminescence (CL) of human leucocytes (HL) after stimulation with opsonized zymosan (C3Z), and extends the findings to peritoneal (RPL) and bronchoalveolar leucocytes (RBAL) collected from actively immunized rats 24 h after i.v. injection of Sephadex. Additionally we demonstrate that NI is a strong inhibitor of proteinase release (PR) from HL. The reference drugs tested for comparison were indomethacin (I), BW 755 C (BW), phenidon (PH), mepacrin (M) and nedrocromil (NE). The rank order of potency for suppression of PR and CL was nearly independent of the cell type and stimulus: PH greater than or equal to BW greater than M greater than NI = 4-OH-NI much greater than I greater than NE. NI was the superior inhibitor of HL activation compared with I as measured either by PR or CL (factor 7), and also of CL of RPL and RBAL (factor 2-3). NI inhibited the PR from HL and CL of RPL or RBAL almost equipotently (IC30: 10-20 micrograms/ml), whereas PH, BW, M and I were 6-10 times more effective as CL inhibitors compared with their PR inhibition. In contrast NE showed a preferential inhibition of PR. This unique inhibition profile on leucocyte activation in vitro may be related to the differences of NI and I which are also existing in their antiinflammatory activities in vivo.