Eotaxin contributes to renal interstitial eosinophilia.
BACKGROUND
A potent eosinophil chemotactic cytokine, human eotaxin, is directly chemotactic for eosinophils. Therefore, the specific expression of eotaxin in tissue might play a crucial role in tissue eosinophilia. However, the precise molecular mechanism of the recruitment and activation of eosinophils in human renal diseases remains to be investigated. We evaluated the role of eotaxin in the pathogenesis of human diffuse interstitial nephritis with marked infiltration of eosinophils.


METHODS
In this study, we examined 20 healthy volunteers. 56 patients with primary or secondary glomerular diseases and two hypereosinophilic syndrome patients without renal involvement. Urinary and serum eotaxin levels were determined by an enzyme-linked immunosorbent assay. We also detected the presence of eotaxin protein immunohistochemically.


RESULTS
On the one hand, urinary levels of eotaxin were significantly higher before the initiation of glucocorticoid administration in the patient with interstitial nephritis with marked infiltration of eosinophils. On the other hand, urinary eotaxin levels were not detected in any patients with nephrotic syndrome, interstitial nephritis without eosinophils, hypereosinophilic syndrome without renal involvement or other renal diseases. Serum eotaxin levels were not detected in any of the patients. Therefore, the detection of eotaxin in the urine was specific for renal interstitial eosinophilia. Moreover, endothelial cells, infiltrating mononuclear cells and renal epithelial cells in the tubulointerstitial lesions were immunostained with specific anti-eotaxin antibodies. Furthermore, the elevated urinary levels of eotaxin decreased dramatically during glucocorticoid-induced convalescence.


OBJECTIVE
We hypothesize that in situ expression of eotaxin may provide a new mechanism to explain the renal interstitial eosinophil infiltration.
First Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
T
T
Wada
K
K
Furuichi
N
N
Sakai
M
M
Shimizu
C
C
Segawa
K
K
Kobayashi
N
N
Mukaida
T
T
Kasahara
K
K
Matsushima
H
H
Yokoyama
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis / Q000652:urine; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000032:analysis* / Q000652:urine; D016207:Cytokines / Q000032:analysis* / Q000097:blood / Q000652:urine; D018450:Disease Progression; D004802:Eosinophilia / Q000473:pathology / Q000503:physiopathology* / Q000652:urine; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000473:pathology / Q000503:physiopathology* / Q000652:urine; D012016:Reference Values
D015415:Biomarkers; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines