Activation of neutrophils in cutaneous T-cell lymphoma

Purpose: CutaneousT-cell lymphoma (CTCL) is a spectrum of disease of unknown etiology defined by infiltrates of activated and malignant Tcells in the skin. In working with blood from CTCL patients, we noticed frequent activation of neutrophils; therefore, we tested the hypothesis that neutrophils are activated in CTCL subjects compared with normal healthy controls. Experimental Design: Using peripheral blood of 44 subjects with CTCL and 15 normal controls, we examined three measures of neutrophil activation. These are the presence of neutrophils of reduced buoyant density, the presence of primed neutrophils in a stimulated chemiluminescence assay, and changes in surface markers by flow cytometry. In addition, we tested plasma interleukin-8 (IL-8) and leukotriene B-4 (LTB4) levels using ELISA. Results: A significantly larger fraction of hypodense neutrophils was observed in CTCL subjects compared with normals (10.6 +/- 1.7% versus 1.5 +/- 0.4%). Stimulated chemiluminescence was also significantly increased in CTCL, and analysis of neutrophil surface markers using flow cytometry showed significantly increased CD11b and CD66b and decreased CD62L, consistent with neutrophil activation. These changes were present even in early stages of CTCL.We further found that plasma IL-8 and LTB4 levels are elevated in CTCL, which could form a feedback loop contributing to disease pathophysiology. Conclusions: CTCL is associated with systemic neutrophil activation, even in early disease, and a feedback loop between neutrophils and Tcells mediated by IL-8 and LTB4 is a potential contribution to the pathophysiology of CTCL.