PRODUCTION OF INTERLEUKIN-8, RANTES AND MCP-1 IN INTRINSIC AND EXTRINSIC ASTHMATICS

The aim of this study was to determine the relative production of chem okines interleukin-8 (IL-8), regulated on activation, normal T-cell ex pressed and secreted (RANTES) and monocyte chemotactic protein-1 (MCP- 1) by intrinsic and extrinsic asthmatics. Nine intrinsic asthmatics, 1 0 extrinsic asthmatics, five nonatopic and fi ve atopic controls under went bronchoalveolar lavage (BAL). Total BAL cells were cultured in th e presence or absence of lipopolysaccharide, Chemokines were measured in BAL cell supernatants and in cell-free bronchoalveolar lavage fluid (BALF) by University of Bristol Division of Medicine enzyme-linked im munoabsorbent assay (ELISA). BAL cell cytospins were stained immunohis tochemically for chemokines. BAL cells from asthmatics produced more I L-8 than controls (statistically significant for extrinsic asthma). RA NTES was elevated in the BAL cell supernatants of four out of nine int rinsic asthmatics as compared to nonatopic controls (not statistically significant), RANTES levels in the BAL cell supernatants of extrinsic asthmatics were all low, MCP-1 production by BAL cells was similar in all groups, Immunostaining of BAL cell cytospins showed the macrophag e to be the predominant positive-staining cell type and correlated wel l with supernatant data, Measurement of chemokines in BALF showed sign ificantly elevated IL-8 in intrinsic asthma compared to nonatopic cont rols, but no increase in extrinsic asthmatics relative to atopic contr ol RANTES was elevated in three out of nine BALFs from intrinsic asthm atics compared with nonatopic controls (not statistically significant) , MCP-1 was not elevated above control levels in BALF of either asthma group. These results suggest an up-regulation in the production of in terleukin-8 and regulated on activation, normal T-cell expressed and s ecreted, but not monocyte chemotactic protein-1 (MCP-1), by macrophage s in the bronchoalveolar lavage of asthmatic subjects, In addition, th e data suggest that regulated on activation, normal T-cell, expressed and secreted, may be differentially produced by macrophages in atopic and nonatopic asthma.