Circulating neutrophils were investigated in 15 patients with
Crohn's disease (CD), 15 with
ulcerative colitis (UC), and 15 healthy volunteers. Dose-response curves for chemotaxis in Boyden chambers were analysed for sensitivity to
leukotriene B4 (
LTB4), its 20-hydroxy-LTB4 (20-OH-LTB4) and 20-carboxy-LTB4 (20-COOH-LTB4) catabolites, and 5- and 15-hydroxyeicosatetraenoic
acids (HETEs). Positive controls included:
complement 5a (C5a), formy-L-methionyl-L-leucyl-
L-phenylalanine (
f-Met-Leu-Phe), and
casein. Control chemotaxis test were performed at concentrations yielding optimal responses in leucocytes of healthy volunteers. Chemotaxis to suboptimal concentrations of
LTB4 1.0 and 3.2 nmol/l, and
5-HETE 316 nmol/l, was markedly depressed in patients with chronic
inflammatory bowel disease (CIBD). Analyses of individual dose-response curves revealed an underlying decreased sensitivity to
LTB4 in 11 out of 30 patients, to
5-HETE in 10 out of 30 patients with a corresponding decrease of median sensitivity to
LTB4 and
5-HETE in both CD and UC. Peak responses to
LTB4,
5-HETE,
f-Met-Leu-Phe, and
casein were identical in the three groups tested, whereas the C5a values were significantly depressed in both groups of patients (p less than 0.05). The potency of
LTB4 exceeded that of
5-HETE by
a factor of approximately 100 whereas 20-OH-LTB4 was nearly as potent as
LTB4. 20-COOH-LTB4 and
15-HETE did not activate chemotaxis of human neutrophils. These findings are suggestive of a competitive inhibition of receptors with heterogeneity for
LTB4 and 5-
HETE.(ABSTRACT TRUNCATED AT 250 WORDS)