Extracorporeal photochemotherapy restores Th1/Th2 imbalance in patients with early stage cutaneous T‐cell lymphoma

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Abstract
Extracorporeal photochemotherapy (ECP) has been shown to be a potent activator of peripheral blood macrophages because it causes a marked release of macrophage‐dependent proinflammatory cytokines, and it is therefore currently considered to be a safe and non‐toxic immunomodulatory treatment. On this basis we studied the function of peripheral blood mononuclear cells (PBMC) in eight patients with early stage (Ib) cutaneous T‐cell lymphoma (CTCL), before and 1 year after ECP, together with their clinical and histological responses. In particular we evaluated in vitro phytohaemagglutinin (PHA)‐stimulated proliferation and production of interleukin‐4 (IL‐4) and interferon‐&ggr; (IFN‐&ggr;) as well as lipopolysaccharide (LPS)‐induced production of IL‐12. Before treatment we observed that PBMC of patients produced significantly higher levels of IL‐4 and lower levels of IFN‐&ggr; and IL‐12 than those of healthy control subjects. After 1 year of ECP, IL‐4, IFN‐&ggr; and IL‐12 production no longer differed from that of control subjects. Moreover, we observed a good clinical result matched by histological response. Our data confirm that early‐ stage CTCL patients show a predominantly type‐2 immune response that might be responsible for several immunological 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 modifier.