TITLE

CIRCULATING TUMOUR NECROSIS FACTOR ALPHA CONCENTRATIONS AND PERIPHERAL CD4[sup +] T CELL CHEMOKINE RECEPTOR EXPRESSION IN PATIENTS WITH PYODERMA GANGRENOSUM

AUTHOR(S)
Brooklyn, T.N.; Williams, A.M.; Probert, C.S.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA61
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Pyoderma gangrenosum (PG) is recognised as an extraintestinal manifestation of inflammatory bowel disease (IBD). Recent reports of PG responding to infliximab suggest that tumour necrosis factor alpha (TNF6) may be important, although in our hands the response of PG to infliximab has been variable. Subsets of CD4[sup +] T cells are functionally polarised according to their cytokine profile and one of the ways of identifying these groups of cells is to examine the chemokine receptors they express. Little is known of the cytokines involved in the development of PG and it is not known whether the disease fits a T-helper type 1 (Th1) or Th2 pattern. Aims: To investigate the hypothesis that, if PG responds to infliximab, TNFoc must be important in the pathogenesis of the disease and it is also likely that PG would display a Th1 phenotype. Patients: Ten patients with PG, half of whom also had underlying IBD, were compared with seven healthy controls. Methods: The concentration of circulating TNFα was determined using enzyme linked immunoadsorbent assay (ELISA). The expression of the chemokine receptors CCR4 and CXCR3 on CD4[sup +] T cells was determined by flow cytometry. The results were compared using the Mann-Whitney U test. Results: The plasma concentrations of TNFα in the PG patients were found to be significantly higher than in the healthy individuals (p=0.002). The expression of CCR4 on CD4[sup +] T cells was significantly higher in the PG patients (p=0.048), but there was no difference in the expression of CXCR3. Conclusions: Plasma concentrations of TNFα in patients with PG are significantly greater than those found in normal individuals, but not as high as those Found in active IBD. Patients with PG preferentially express CCR4 not CXCR3 on peripheral CD4[sup +] T cells, suggesting that PG may be a Th2 disease. These Findings may explain the variable clinical response to infliximab.
ACCESSION #
9747701

 

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