The effect of aspirin on mononuclear cells in aspirin-sensitive asthmatics

Three groups, comprising normal subjects (n = 10), aspirin-sensitive asthmatics (ASA+; n = 10) and aspirin-insensitive asthmatics (ASA-; n = 10) were entered into a blinded, parallel group study to assess the modulating effect of aspirin (ASA; 0.0275, 0.275, 1.385, 2.75, 6.9, 13.8 and 27.5 muM) on lymphocyte proliferation in vitro, either alone or in combination with the mitogen, phytohemagglutinin (PHA; 10, 25, 50, 100, 200 and 500 mug/ml). The percentage and absolute numbers of CD4-positive T cells (normals: 51.3%; ASA+: 51.1%; ASA-: 46.1%; p = 0.4038) and CD8-positive T cells (normal: 27.5%; ASA+: 26.4%; ASA-: 28.4%; p = 0.8408) did not differ significantly between the groups. Significant differences in mean PHA responses between ASA+, ASA- and normal subjects were observed when peripheral blood lymphocytes (PBL) were exposed to PHA concentrations over the range 10-50 mug/ml; PHA 10 mug/ml (p <0.005), PHA 25 mug/ml (p <0.005) and PHA 50 mug/ml (p <0.01), the lowest and highest proliferative responses being obtained with PBL from ASA+ and ASA-, respectively. However, at higher PHA concentrations (100-500 mug/ml), differences between the three groups were not observed. When ASA was added in combination with PHA, augmentation of the PHA response was observed with cells from all three groups but was most marked in the ASA+ group, especially at lower PHA concentrations (10-50 mug/ml) in combination with 0.275-13.8 muM ASA. When ASA was added alone, significant proliferation was obtained with cells from normal subjects at a concentration of 6.9 muM, while 13.8 and 27.5 muM were required to produce proliferation in ASA+ and ASA-. When these data were analysed further, a subset (n = 9) of ASA responders was identified of whom the majority (n = 5) were ASA+ (p <0.05). This study suggests that ASA not only enhances lymphocyte proliferation in response to PHA but also induces proliferation per se. Although the mechanisms involved are unclear, the data indicate that further study of lymphocytes from both ASA+ and ASA- may be warranted.