Neutrophil-related immunoinflammatory disturbance in steroid-overdosed ulcerative colitis patients.
BACKGROUND
There is some evidence that large preoperative doses of steroids are a causative factor for postoperative higher morbidity in ulcerative colitis (UC) patients. This study aimed to assess steroid-related changes in functional profiles of neutrophils in UC patients to estimate the immunological changes under surgical stress.


METHODS
Neutrophils were extracted from peripheral blood of 30 UC patients and 30 healthy controls. UC patients whose neutrophils were isolated were divided into two subgroups according to their total preoperative dosage of prednisolone: group H, > or =10,000 mg; group L, <10,000 mg. Expression of neutrophil surface antigens was analyzed and neutrophil phagocytosis was evaluated. Patterns of cell death of neutrophils were evaluated by co-culturing with Escherichia coli. Production of inflammatory mediators in cultured neutrophils was assessed.


RESULTS
There were no significant differences in the expression rates of TLR4, CD11b, and CD16b on neutrophils (CD15(+) cells) between the two patient groups and controls. There was also no significant difference in neutrophil phagocytosis between the two patient groups and controls. The neutrophil necrosis rate in group H was higher than that in group L and the controls 3 h after exposure to E. coli. Neutrophils from group H released the highest levels of proinflammatory cytokines following interleukin-1beta or lipopolysaccharide stimulation. Neutrophils from group H also released the highest levels of proteolytic enzymes.


CONCLUSIONS
Steroid-overdosed UC patients may have a functional deficit in neutrophils, which may cause a postsurgical systemic "storm" of inflammatory mediators.
Yoshiyama
Shigeyuki
S
Department of Gastrointestinal Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan.
Miki
Chikao
C
Okita
Yoshiki
Y
Araki
Toshimitsu
T
Uchida
Keiichi
K
Kusunoki
Masato
M
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology; D011239:Prednisolone / Q000008:administration & dosage*
D016207:Cytokines; D005938:Glucocorticoids; D008565:Membrane Proteins; D011239:Prednisolone