THE TISSUE EXPRESSION OF CYTOKINES IN HUMAN ACUTE CUTANEOUS GRAFT-VERSUS-HOST DISEASE

Although acute graft-versus-host disease (GVHD) is a common complicati on after allogeneic bone marrow transplantation (BRIT), the specific p athophysiology of tissue damage has not been elucidated, We have previ ously described an infiltrate of CD2+, CD8+, alpha/beta receptor(+) T lymphocytes, and the upregulation of ICAM-1 in tissues with acute GVHD , We hypothesized that these infiltrating lymphocytes may secrete cyto kines that could contribute to tissue damage, In the current study, we used reverse transcription (RT) polymerase chain reaction (PCR) to ex plore the mRNA expression of candidate inflammatory cytokines IL-1 alp ha, IL-2, IL-4, IL-6, TNF-alpha, and interferon-gamma (IFN-gamma) in p eripheral blood mononuclear cells (PBMC) and skin biopsies of allogene ic BRIT patients with GVHD and controls, In post-BMT control PBMC (n=1 0), IL-2 RNA was infrequent (20% of samples) but was significantly mor e frequently detectable (71%; P<0.05) after development of acute GVHD (n=7), IL-4 expression was also more common in PBMC from patients with acute GVHD (57% vs, 30%; P<0.05), Consistent with the PBMC data, IL-2 and IL-4 RNA were also more frequently detectable in skin biopsies wi th GVHD (n=10): 70% of samples expressed IL-2 vs, 25% of normal contro ls (n=8; P<0.05); 60% had detectable IL-4 RNA vs, O% of controls (P<0. 05). IFN-gamma detectability (40% vs, 12%; P<0.05) was also more frequ ent in GVH skin, For both PBMC and skin, IL-1 alpha expression was inf requent in GVHD and controls, whereas TNF-alpha and IL-6 were expresse d in nearly all samples, These data suggest that upregulated expressio n of IL-2, IL-4, and IFN-gamma may be part of the inflammatory cascade of human acute GVHD, while IL-1 alpha, TNF-alpha, and IL-6 are not di scriminatory for the inflammation observed at the time of initial GVHD diagnosis.