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 phenotype consistent with T cell suppressive activity. Analysis of the immunopathology in endobronchial biopsies from asthmatic subjects has revealed significantly reduced proportions of suppressive macrophage populations associated with chronic T-cell mediated inflammation.


OBJECTIVE
This study investigates whether the altered homeostasis within the lung macrophage populations in asthma is reflected in aberrant differentiation of peripheral blood monocytes and whether this differentiation may be influenced by IL-10.


METHODS
Monocytes from 14 normal individuals and 14 atopic asthmatics were grown in culture for 7 days in the presence or absence of IL-10, added on day 5. Double immunofluoresence studies were performed on cytospins of the differentiated macrophages using the monoclonal antibodies RFD1 and RFD7 to distinguish inductive and suppressive macrophages by their respective phenotypes. HLADR expression was quantified using the monoclonal antibody RFDR1. Macrophage function was determined by quantifying allostimulation in a mixed leucocyte reaction and by measuring TNFalpha and TGFbeta production.


RESULTS
With no cytokine addition the proportion of maturing macrophages 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% increase) being significantly greater than that in normal subjects (32% increase) (P<0.01). Asthmatic monocytes had a greater effect in stimulating MLR than normals (P < 0.05) but the addition of IL-10 reduced T cell proliferation in an MLR to a equivalent level in both groups.


CONCLUSIONS
These results suggest that a fundamental problem may exist in the differentiation of monocytes in asthma which may be reversed by IL-10.
Department of Clinical Immunology, Royal Free Hospital School of Medicine, London, UK.
V J
VJ
Tormey
C
C
Leonard
J
J
Faul
S
S
Bernard
C M
CM
Burke
L W
LW
Poulter
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006684:HLA-DR Antigens / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D016676:Macrophages, Alveolar / Q000502:physiology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D006684:HLA-DR Antigens; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10