The role of micro-inflammation in the pathogenesis of uraemic pruritus in haemodialysis patients.
BACKGROUND
Uraemic pruritus (UP) is still one of the most vexing and disabling symptoms in chronic renal failure. The pathogenesis of UP is obscure and effective therapeutic strategies are elusive. Deduced from partial successful treatment modalities, there is evidence that an alteration of the immune system with a pro-inflammatory pattern along with a deranged T-helper-cell differentiation may be involved in the pathogenesis of UP. We, therefore, investigated whether UP is related to an augmented Th1-differentiation as measured by determination of intracytoplasmatic (i.c.) cytokines and expression of chemokine receptors. Additionally, pro-inflammatory cytokines were determined in serum.


METHODS
In a multicentre study, 171 patients on haemodialysis (HD) were screened for UP. Finally, 13 HD patients with and 13 HD patients without UP, as well as 15 healthy controls were enrolled in the study. Peripheral blood mononuclear cells were isolated and the proportion of Th1- and Th2-cells was determined by flow cytometry. The expression of chemokine receptors on CD4 cells (CXCR3 preferentially on Th1 and CCR4 on Th2) and i.c. cytokines (IFNgamma for Th1 and IL4 for Th2) were measured after in vitro stimulation. Serum cytokine levels (IL6 and TNFalpha) and CRP were measured by ELISA.


RESULTS
Compared to HD patients without UP, those complaining of UP showed a significantly enhanced proportion of Th1-cells as measured by both techniques. Additionally, serum CRP and IL6 levels were significantly higher in HD patients with UP, compared to HD patients without UP.


CONCLUSIONS
These results point to a central role of inflammation in the pathogenesis of UP in HD patients.
Kimmel
Martin
M
Division of General Internal Medicine and Nephrology, Department of Internal Medicine, Robert-Bosch Hospital, Germany. vm.kimmel@t-online.de
Alscher
Dominik Mark
DM
Dunst
Robert
R
Braun
Niko
N
Machleidt
Christoph
C
Kiefer
Thomas
T
Stülten
Christina
C
van der Kuip
Heiko
H
Pauli-Magnus
Christiane
C
Raub
Ulrich
U
Kuhlmann
Ulrich
U
Mettang
Thomas
T
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011537:Pruritus / Q000097:blood / Q000209:etiology* / Q000276:immunology; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000097:blood; D006435:Renal Dialysis; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014511:Uremia / Q000150:complications* / Q000628:therapy
D015415:Biomarkers; C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D015850:Interleukin-6; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha