title: Cytokine replacement in patients with HIV-1 non-Hodgkin's lymphoma: the rationale for low-dose interleukin-2 therapy.
abstract: OBJECTIVE
  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 critical 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 immune deficiencies could be corrected by cytokines delivered at doses that result in near-physiologic concentrations in vivo.
  
  
  METHODS
  We have used the severe combined immune deficient mouse engrafted with human peripheral blood leukocytes from healthy individuals who are seropositive for the Epstein-Barr virus to study the spontaneous development of malignant Epstein-Barr virus-positive human B-cell lymphoproliferative disorder.
  
  
  RESULTS
  We have demonstrated in this model that, in the absence of CD4+ T cells, cytokine replacement with low-dose interleukin (IL)-2 therapy can prevent Epstein-Barr virus-positive human B-cell lymphoproliferative disorder by interacting with mouse natural killer and human CD8+ T cells. We review our clinical experience with administration of low-dose IL-2 therapy in patients with HIV-1-related cancer, noting minimal toxicity and significant immune modulation. We provide evidence that this therapy can favorably alter the type 1 cytokine profile in vivo in these patients, and improve the cellular response to infectious insults in vitro.
  
  
  CONCLUSIONS
  Early clinical studies with low-dose IL-2 therapy in patients with HIV-1-related lymphoma suggest that this therapy may have a role in the prevention and treatment of this disease.
authors.affiliation: Division of Hematology/Oncology, The Arthur G. James Cancer Hospital and Solove Research Institute, Columbus, Ohio, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Shah
authors.forename: R A
authors.initials: RA
authors.lastname: Baiocchi
authors.forename: T A
authors.initials: TA
authors.lastname: Fehniger
authors.forename: V P
authors.initials: VP
authors.lastname: Khatri
authors.forename: M
authors.initials: M
authors.lastname: Gould
authors.forename: B
authors.initials: B
authors.lastname: Poiesz
authors.forename: Z P
authors.initials: ZP
authors.lastname: Bernstein
authors.forename: M A
authors.initials: MA
authors.lastname: Caligiuri
mesh_terms: D000818:Animals; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D016483:Lymphoma, AIDS-Related / Q000276:immunology / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID
chemical_list: D007376:Interleukin-2; D007371:Interferon-gamma