ALTERATION IN THE PRODUCTION OF FREE OXYGEN RADICALS AND PROINFLAMMATORY CYTOKINES BY PERITONEAL AND ALVEOLAR MACROPHAGES IN OLD MICE AND IMMUNOMODULATORY EFFECT OF RU-41740 ADMINISTRATION PART-I - EFFECT OF SHORT AND REPETITIVE NOISE STRESS

The aim of this study was to analyze the effects of stress on natural immunity in old mice, and the potential of an immunomodulating drug to correct stress-induced immune abnormalities. We analyzed both the alv eolar (ALM) and peritoneal macrophage (PerM) oxidative responses and c ytokine productions of TNF-alpha and IL-1 alpha,in old mice after expo sure to 3 days of noise stress, with and without treatment with RU 417 40, an immunomodulating compound. Production of Free Oxygen Radicals ( FOR) by ALM and PerM macrophages was evaluated using a luminol-depende nt chemiluminescence method at the basal state and after stimulation. Serum corticosterone was also measured. Three groups of 22-24 month-ol d C57BL/6 mice were studied. Seven mice were treated with RU 41740 (10 mg kg(-1)) every day for 5 days and then exposed to sound stress (110 dB, 1000 Hz, for 3 nights). Ten mice were treated with saline, then s ubmitted to a sham stress. Eight animals received neither treatment no r stress. There was no difference in corticosterone level between the three groups and between these groups and a control group nonstressed, noncannulated. After stimulation by fMetLeuPhe, production of FOR by ALM and PerM significantly increased after stress and returned to norm al values after RU 41740 treatment(p < 0.001). The cytokine levels (TN F-alpha and IL-1 alpha) decreased after stress and returned to normal levels after RU 41740 treatment. This study shows that, in aged mice, auditory stress is associated with modifications of macrophage functio ns which are different, depending on their localization and on the fun ction under study. It confirms the immunomodulatory capacities of RU 4 1740 that was shown to counteract these effects of stress in elderly a nimals, (C) 1998 Elsevier Science B.V.