The role of different cytokines and cells of immune system
in the pathogenesis of chronic GVHD (cGVHD) is still
controversial. Earlier studies, which were either retrospective
or analysed one or a few factors, did not show
unequivocal results. We prospectively evaluated cytokine
levels and lymphocyte subsets in 30 patients who underwent
Allo-SCT to investigate their possible correlation
with cGVHD. Levels of IL-4, IL-6, IL-10, IFN-c, tumour
necrosis factor-alpha (TNF-a) and its soluble receptors
were assessed by ELISA in 30 patients at different times
after SCT. Lymphocyte subsets were evaluated by flow
cytometry in peripheral blood at the same times as
cytokines. A multivariate analysis was performed using
principal component analysis and multi-factor ANOVA
(analysis of variance). Eighteen patients developed
cGVHD at a median time of 6 months (range, 5–9) after
SCT. In multivariate analysis, we observed a correlation
between cGVHD and clusters of cytokines and lymphocyte
subsets from the third to the sixth month after SCT.
These clusters changed their composition over time,
but they constantly included natural killer (NK) and
CD152þ T cells as negative predictors of cGVHD.
TNF-a prevailed among other cytokines before the onset
of cGVHD. This prevalence could be related partly to the
defect of immunoregulatory cells