Increased levels of specific leukocyte- and platelet-derived substances during normal anti-tetanus antibody synthesis in patients with inactive Crohndisease
Hj. Nielsen et al., Increased levels of specific leukocyte- and platelet-derived substances during normal anti-tetanus antibody synthesis in patients with inactive Crohndisease, SC J GASTR, 36(3), 2001, pp. 265-269
Background: Crohn disease is considered a consequence of inappropriate upre
gulation of immune reactions evoked by the intestinal microflora or luminal
antigens. Since the intestinal mucosa is continuously exposed to tetanus t
oroid we studied the antibody response to tetanus toroid booster immunizati
on in patients with Crohn disease and the subsequent release of various inf
lammatory mediators and growth factors in blood. Methods: Ten patients with
inactive disease and no concurrent medication and 12 age-and gender-matche
d healthy volunteers with anti-tetanus antibody levels less than 0.1 IU/ml
were inoculated with 1 ml (6 Lf units) of tetanus toroid vaccine. The anti-
tetanus antibody levels were determined in serum obtained before inoculatio
n and after 7, 14 and 28 days, respectively. C-reactive protein (CRP), inte
rleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), histamine, Vasc
ular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinas
es-1 (TIMP-1), plasminogen activator inhibitor type-1 (PAI-1) and myelopero
xidase (MPO) were determined in serum or plasma obtained on the same days.
Results: After inoculation anti-tetanus antibody levels were equally raised
in patients and healthy volunteers. Pre-inoculation CRP levels were below
the upper level of the normal range (< 10 mg/l) in all inoculated patients/
volunteers. No differences in IL-6, TNF-<alpha>, MPO or histamine levels be
tween patients and healthy volunteers were observed. CRP levels were within
the normal range and IL-6, TNF-alpha, MPO and histamine levels were unchan
ged in patients and volunteers during the study period. The levels of VEGF,
TIMP-1 and PAI-1 were unchanged in the healthy volunteers during the study
period, but were significantly (P < 0.05) increased at day 14 in patients
with Crohn disease. At day 28 the levels had fallen to pre-inoculation leve
ls, apart from PAI-1, which was still significantly (P < 0.05) increased. C
onclusions: In patients with inactive Crohn disease, booster immunization a
gainst tetanus toroid seems to result in normal anti-tetanus antibody synth
esis, but it may cause inappropriate release of certain bioactive substance
s, which are known to play a major role in modulation of the inflammatory r
esponse.