Cytokines in tear fluid of patients with ocular graft-versus-host disease after allogeneic stem cell transplantation

PURPOSE To investigate the profile of cytokines in tear fluid of patients after allogeneic stem cell transplantation (allo-SCT) and determine their relation to the presence and manifestations of ocular graft-versus-host disease (GvHD). METHODS In this cross sectional study tear fluid was collected in 34 consecutive adult patients that previously underwent allo-SCT (16 with ocular GvHD and 18 without) and 16 age- and gender-matched healthy controls using the Schirmer test under local anesthesia. Tear fluid was analyzed by multiplex immunoassay for the presence of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ. Levels of measured cytokines were correlated with the findings in slit lamp examination and the Ocular Surface Disease Index (OSDI). RESULTS The levels of IL-6 and IFN-γ in tear fluid in ocular GvHD patients were significantly elevated in comparison to patients without ocular GvHD and healthy controls (p<0.005 for each) The levels of IFN-γ correlated with the Schirmer score (r=-0.48, p<0.0001) and tear break up time (TBUT; r=-0.38, p=0.03). Tear IL-6 levels correlated with complaints of dry eyes (r=0.39, p=0.02), tear production (r=-0.59, p<0.0001), fluorescent staining of the cornea (r=0.42, p=0.01), and with the OSDI score (r=0.40, p=0.005). CONCLUSIONS IL-6 and IFN-γ were elevated in tear fluid of patients with ocular GvHD and correlated with different symptoms of dry eye disease, suggesting that IFN-γ is elevated during the early stages and IL-6 is involved in later stages of ocular GVHD and exhibits moreover an association with its severity.