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

Abstract

Crohn disease is considered a consequence of inappropriate upregulation of immune reactions evoked by the intestinal microflora or luminal antigens. Since the intestinal mucosa is continuously exposed to tetanus toxoid we studied the antibody response to tetanus toxoid booster immunization in patients with Crohn disease and the subsequent release of various inflammatory mediators and growth factors in blood. Ten patients with inactive disease and no concurrent medication and 12 age-and gender-matched healthy volunteers with anti-tetanus antibody levels less than 0.1 IU/ml were inoculated with 1 ml (6 Lf units) of tetanus toxoid vaccine. The anti-tetanus antibody levels were determined in serum obtained before inoculation and after 7, 14 and 28 days, respectively. C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), histamine, vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinases-1 (TIMP-1), plasminogen activator inhibitor type-1 (PAI-1) and myeloperoxidase (MPO) were determined in serum or plasma obtained on the same days. 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 between patients and healthy volunteers were observed. CRP levels were within the normal range and IL-6, TNF-alpha, MPO and histamine levels were unchanged 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 levels, apart from PAI-1, which was still significantly (P<0.05) increased. In patients with inactive Crohn disease, booster immunization against tetanus toxoid seems to result in normal anti-tetanus antibody synthesis, but it may cause inappropriate release of certain bioactive substances, which are known to play a major role in modulation of the inflammatory response.