Suppression of inflammatory cytokine secretion by granulocyte/monocyte adsorptive apheresis in active ulcerative colitis.
To elucidate the molecular mechanisms involved in the therapeutic effects of granulocyte/monocyte adsorption apheresis, changes were investigated in the cytokine responses of peripheral blood mononuclear cells (PBMC) before and after granulocyte/monocyte adsorptive apheresis in ulcerative colitis (UC) patients. Four patients with active UC were enrolled. All patients responded to granulocyte/monocyte adsorptive apheresis. A total of 20 sessions of four patients were analyzed. Peripheral blood mononuclear cells were isolated from peripheral venous blood within 5 min before and after each session of granulocyte/monocyte adsorptive apheresis. The cells were stimulated with interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha for 24 h, and the secreted IL-8 and IL-6 levels were determined by enzyme-linked immunosorbent assay (ELISA). IL-1beta-induced IL-8 and IL-6 secretion was significantly decreased after granulocyte/monocyte adsorptive apheresis. TNF-alpha-induced IL-8 secretion was also significantly decreased after apheresis, but there was no significant difference in TNF-alpha-induced IL-6 secretion (P = 0.052). In conclusion, granulocyte/monocyte adsorptive apheresis down-regulates the IL-1beta- and TNF-alpha-induced inflammatory responses in PBMC. The induction of hyporesponsiveness to pro-inflammatory cytokines may be an important factor mediating the clinical effects of granulocyte/macrophage adsorptive apheresis in UC patients.
Andoh
Akira
A
Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan. andoh@belle.shiga-med.ac.jp
Tsujikawa
Tomoyuki
T
Inatomi
Osamu
O
Deguchi
Yasuyuki
Y
Hata
Kazunori
K
Kitoh
Katsuyuki
K
Sasaki
Masaya
M
Mitsuyama
Keiichi
K
Fujiyama
Yoshihide
Y
D000328:Adult; D001781:Blood Component Removal / Q000379:methods; D003093:Colitis, Ulcerative / Q000097:blood / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000473:pathology / Q000628:therapy; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha