DYSREGULATION OF MONOCYTE DIFFERENTIATION IN ASTHMATIC SUBJECTS IS REVERSED BY IL-10

Background IL-10 can modulate the differentiation of normal monocytes to macrophages, increasing the proportion of maturing cells with a phe notype consistent with T cell suppressive activity. Analysis of the im munopathology in endobronchial biopsies from asthmatic subjects has re vealed significantly reduced proportions of suppressive macrophage pop ulations associated with chronic T-cell mediated inflammation. Objecti ve This study investigates whether the altered homeostasis within the lung macrophage populations in asthma is reflected in aberrant differe ntiation of peripheral blood monocytes and whether this differentiatio n may be influenced by IL-10. Methods Monocytes from 14 normal individ uals and 14 atopic asthmatics were grown in culture for 7 days in the presence or absence of IL-10, added on day 5. Double immunofluorescenc e studies were performed on cytospins of the differentiated macrophage s using the monoclonal antibodies RFD1 and RFD7 to distinguish inducti ve and suppressive macrophages by their respective phenotypes. HLADR e xpression was quantified using the monoclonal antibody RFDR1. Macropha ge function was determined by quantifying allostimulation in a mixed l eucocyte reaction and by measuring TNF alpha and TGF beta production. Results With no cytokine addition the proportion of maturing macrophag es with a suppressive phenotype (D1(+)D7(+)) at day 7 was lower in the asthmatic samples (18%) compared with normals (25%). IL-10 increased the proportion of suppressive cells in cultures of both asthmatic and normal monocytes with the increase in the asthmatic subjects (94% incr ease) being significantly greater than that in normal subjects (32% in crease) (P<0.01). Asthmatic monocytes had a greater effect in stimulat ing MLR than normals (P < 0.05) but the addition of IL-10 reduced T ce ll proliferation in an MLR to a equivalent level in both groups.Conclu sions These results suggest that a fundamental problem may exist in th e differentiation of monocytes in asthma which may be reversed by IL-1 0.