Suppression of interleukin-1beta- and tumor necrosis factor-alpha-induced inflammatory responses by leukocytapheresis therapy in patients with ulcerative colitis.
BACKGROUND
To elucidate the molecular mechanisms involved in the therapeutic effects of leukocytapheresis (LCAP), we investigated the alterations in the cytokine responses of peripheral blood mononuclear cells (PBMCs) before and after LCAP therapy in ulcerative colitis (UC) patients.


METHODS
Twelve patients with UC who did not respond to steroid therapy were enrolled. Nine patients responded to LCAP therapy, but 3 patients did not show clinical improvement. PBMCs were isolated from peripheral venous blood obtained within 5 min before and after the first and second session of LCAP treatment. Cells were stimulated with interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha for 24 h, and the levels of secreted IL-8 and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA).


RESULTS
LCAP induced a significant decrease in peripheral lymphocyte, monocyte, and platelet counts. IL-1beta- and TNF-alpha-induced IL-8 and IL-6 secretion was significantly decreased after the first and second LCAP treatments. These responses were associated with inhibitory effects on nuclear factor (NF)-kappaB DNA-binding activity.


CONCLUSIONS
LCAP downregulates the IL-1beta- and TNF-alpha-induced inflammatory responses in PBMCs isolated from UC patients. The induction of hyporesponsiveness to proinflammatory cytokines may be an important factor mediating the clinical effects of LCAP in UC patients.
Andoh
Akira
A
Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu, 520-2192, Japan.
Ogawa
Atsuhiro
A
Kitamura
Ken-ichi
K
Inatomi
Osamu
O
Fujino
Sanae
S
Tsujikawa
Tomoyuki
T
Sasaki
Masaya
M
Mitsuyama
Keiichi
K
Fujiyama
Yoshihide
Y
D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha