Cytokine gene expression in skin and lymphoid organs in graft versus host disease

Abstract

Aim - To determine if human graft versus host disease (GvHD) is associated with any detectable change in cytokine gene expression in the skin and lymphoid organs. Methods - Reverse transcriptase and the polymerase chain reaction were used to amplify mRNA for interleukins-1 (IL-1), -2 (IL-2), -4 (IL-4) and -6 (IL-6), IL-2 receptor (IL-2R), tumour necrosis factors α (TNF-α) and β (TNF-β), gamma interferon (IFNγ) and granulocyte macrophage colony stimulating factor (GM-CSF) in frozen punch biopsy specimens of skin and necropsy samples of skin, lymph node, and spleen. Results - No cytokine mRNA was detected in the punch biopsy specimens except weak signals for IL-6 and IL-1 and GM-CSF in two normal donors and IL2-R in one patient with GvHD. In samples of skin taken at necropsy, however, significant quantities of mRNA for TNF-α, TNF-β, and IL-4 were detected in patients who had or had had GvHD in contrast to those without the disease whose skin lacked mRNA for these products but contained detectable quantities of IL-1, IL2-R, IL-6 and GM-CSF. There seemed to be a reciprocal relation between TNF-α and IL-4. In necropsy samples of lymph node and spleen a pattern of cytokine production similar to that in the skin was observed with a preponderance of TNF-α, TNF-β and IL-4 in patients with GvHD and GM-CSF and IL-6 in those without the disease. Conclusions - The local synthesis of these molecules would explain many of the morphological and immunohistological features of GvHD. The failure to detect TNF-α, TNF-β, and IL-4 in skin biopsy specimens exhibiting GvHD is probably due to their small size but further investigations are required.