Increased levels of specific leukocyte- and platelet-derived substances during normal anti-tetanus antibody synthesis in patients with inactive Crohndisease

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.