Whole blood chemiluminescence as a systemic inflammatory parameter in asthma.

Blood phagocytes from patients with asthma not treated with antiinflammatory drugs have an increased capacity to produce reactive oxygen metabolites. We studied the phenomenon in a group of patients with asthma receiving inhaled steroids with whole blood chemiluminescence (CL), a simple reactive oxygen metabolite assay suitable for routine use. There was no difference in CL values between patients with stable asthma and no current obstruction (n = 19; mean CL +/- SD = 26.01 +/- 6.51 mV x min) and healthy control subjects (n = 20; mean CL +/- SD = 27.37 +/- 6.15 mV x min), whereas the patients with asthma and current obstruction (n = 27) had significantly higher CL responses (mean CL +/- SD = 41.10 +/- 14.79 mV x min) than both the patients with nonobstructive asthma and the healthy control subjects (p < 0.0005). There was a negative correlation between whole blood CL and the forced expiratory volume in 1 second of the patients with asthma (Spearman's r = -0.47). When the CL values were corrected for the number of phagocytes present in the reactions, the patients with nonobstructive asthma had significantly lower values than the healthy control subjects (p < 0.05). We suggest that the CL values of the patients with nonobstructive asthma reflect the result of effective antiinflammatory treatment and that whole blood CL may be useful as a systemic parameter in the follow-up of the inflammatory process in asthma.

Increased mineral dust-induced production of reactive oxygen species by blood monocytes from patients with malignant diseases.

Mononuclear leukocytes were isolated from the peripheral blood of 15 patients with malignant pulmonary diseases, 17 patients with pulmonary infections, 18 patients with chest film abnormalities of non-malignant, non-infectious etiology, and 15 healthy persons. The cells were exposed to zymosan yeast, BCG vaccine, quartz, or chrysotile asbestos, and the subsequent production of reactive oxygen species (ROS) was measured by luminol-dependent chemiluminescence. All the stimulants caused significantly higher ROS production in the patient groups than in the healthy control group, and the asbestos-induced ROS production was significantly more pronounced in the cancer group than in the two non-cancer patient groups combined. After one-year follow-up, 5 of the 15 cancer patients were alive, and these patients had significantly lower mineral dust-induced ROS responses at the time of diagnosis than were found in the patients who died. This result was verified in a subsequent study comprising 19 patients with malignant pulmonary disorders (6 alive after one year). In conclusion, monocytes from patients with malignant diseases seem to be primed for an increased ROS production, and high ROS responses seem to correlate with a poor one-year survival of the patients.

A synergistic interaction between Bacillus Calmette-Guérin (BCG) and NADPH oxidase stimulants on the production of reactive oxygen metabolites by human mononuclear phagocytes.

Bacillus Calmette-Guérin (BCG) was added simultaneously with known NADPH oxidase stimulants to suspensions of human mononuclear leukocytes, and the subsequent production of reactive oxygen metabolites (ROMs) was studied by luminol-dependent chemiluminescence. BCG significantly amplified the ROM responses induced by zymosan, phorbol myristate acetate (PMA), and quartz, but not by concanavalin A and asbestos fibers. The stimulatory effect occurred rapidly when BCG was added to cells already phagocytosing zymosan, and vanished rapidly when extracellular BCG was removed from adherent monocyte cultures by washing prior to the addition of zymosan. The stimulatory effect of BCG could not be reproduced with recombinant interferon-gamma, tuberculin PPD, muramyl dipeptide, nor with the apathogenic Mycobacterium tuberculosis strain RV37. BCG and zymosan or PMA that had been incubated together prior to addition to the mononuclear cell suspensions caused ROM production with faster kinetics than if the reagents were added separately without preincubation. In conclusion, the synergy between BCG and some of the NADPH oxidase stimulants seems to be due to an interaction between BCG and the NADPH oxidase stimulants rather than to an interaction between BCG and the ROM-producing cells. Such interactions between mycobacteria and NADPH oxidase stimulants may be of importance as a factor affecting the individual susceptibility to tissue damage in tuberculosis, for example in silicotuberculosis.