Cytokine replacement in patients with HIV-1 non-Hodgkin's lymphoma: The rationale for low-dose interleukin-2 therapy

PURPOSE The drastic increase in the incidence of non-Hodgkin's lymphoma in patients infected with HIV-1 is testimony to the fact that our immune system is cri tical for the prevention of certain malignancies. Preclinical and clinical studies were conducted to (1) gain further insight into defects in immunity that can lead to malignant transformation and (2) determine if certain imm une deficiencies could be corrected by cytokines delivered at doses that re sult in near-physiologic concentrations in vivo. METHODS We have used the severe combined immune deficient mouse engrafted with huma n peripheral blood leukocytes from healthy individuals who are seropositive for the Epstein-Barr virus to study the spontaneous development of maligna nt Epstein-Barr virus-positive human B-cell lymphoproliferative disorder. RESULTS We have demonstrated in this model that, in the absence of CD4+ T cells, cy tokine replacement with low-dose interleukin (IL)-2 therapy can prevent Eps tein-Barr virus-positive human B-cell lymphoproliferative disorder by inter acting with mouse natural killer and human CD8+ T cells. We review our clin ical experience with administration of low-dose IL-2 therapy in patients wi th HIV-1-related cancer, noting minimal toxicity and significant immune mod ulation. We provide evidence that this therapy can favorably alter the type 1 cytokine profile in vivo in these patients, and improve the cellular res ponse to infectious insults in vitro. CONCLUSION Early clinical studies with low-dose IL-2 therapy in patients with HIV-1-re lated lymphoma suggest that this therapy may have a role in the prevention and treatment of this disease.