EXTRACORPOREAL PHOTOCHEMOTHERAPY RESTORES TH1 TH2 IMBALANCE IN PATIENTS WITH EARLY-STAGE CUTANEOUS T-CELL LYMPHOMA/

Extracorporeal photochemotherapy (ECP) has been shown to be a potent a ctivator of peripheral blood macrophages because it causes a marked re lease of macrophage-dependent proinflammatory cytokines, and it is the refore currently considered to be a safe and non-toxic immunomodulator y treatment. On this basis we studied the function of peripheral blood mononuclear cells (PBMC) in eight patients with early stage (Ib) cuta neous T-cell lymphoma (CTCL), before and 1 year after ECP, together wi th their clinical and histological responses. In particular we evaluat ed in vitro phytohaemagglutinin (PHA)-stimulated proliferation and pro duction of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) as we ll as lipopolysaccharide (LPS)-induced production of IL-12. Before tre atment we observed that PBMC of patients produced significantly higher levels of IL-4 and lower levels of IFN-gamma, and IL-12 than those of healthy control subjects. After 1 year of ECP, IL-4, IFN-gamma and IL -12 production no longer differed from that of control subjects. Moreo ver, we observed a good clinical result matched by histological respon se. Our data confirm that early-stage CTCL patients show a predominant ly type-2 immune response that might be responsible for several immuno logical abnormalities found in this disease. We have demonstrated that ECP reverses the T-helper type 1/T-helper type 2 (Th1/Th2) imbalance and may therefore be considered an efficient biological response modif ier.