Antiproliferative effects of interleukin-4 on freshly isolated non- Hodgkin malignant B-lymphoma cells

Abstract

The pattern of in vitro growth response of freshly isolated non-Hodgkin malignant lymphoma B cells (NHML) to cytokines was investigated. Ten tumor specimens of low- or intermediate-grade malignancy were selected for study. To assess their proliferative capacity in vitro, B-lymphoma cells were activated through ligation of their surface Ig receptor with insolubilized anti-IgM antibodies or Staphylococcus aureus strain Cowan I (SAC). In the great majority of cases, interleukin-2 (IL-2) was the sole factor that significantly and reproducibly stimulated DNA synthesis in NHML activated through their surface Igs. Other B-cell tropic factors, including IL-4, IL-5, IL-6, and tumor necrosis factor- alpha (TNF-alpha), failed to elicit a growth response in most of the IL- 2-responsive neoplastic samples. However, one specimen among 10 exhibited the opposite pattern of response and proliferated following culture with IL-4 and anti-Ig reagents, but not after IL-2 stimulation. Three specimens could also be induced for DNA synthesis on cross- linking of their surface Igs in the absence of exogenous growth factors. Although IL-4 could not support the in vitro growth of the majority of NHML cases, it strongly suppressed the proliferative signals delivered to these cells by anti-Ig reagents used alone or in combination with IL-2. Our data suggest that, in most cases, IL-4 essentially provides growth-inhibitory signals to NHML when they are activated through their surface Ig receptors and as such may be considered to be a valid candidate for future therapy of this type of mature B-cell malignancy.

Analysis of the involvement of cytokines in allergy and breast cancer association

“…Several lines of evidence suggest that IL-4, produced mainly by Th2 lymphocytes, could display antitumor activity. IL-4 suppresses cancer development through stimulation of B cell differentiation and IgE synthesis, as well as proliferation of antigen-specific cytotoxic T lymphocytes [ 34 ]. Tepper et al .…”

Lycopene Enhances Antioxidant Enzyme Activities and Immunity Function in N-Methyl-N′-nitro-N-nitrosoguanidine–Induced Gastric Cancer Rats

“…Interleukin-2 (IL-2) or aldesleukin is used to treat skin melanomas and kidney cancer. IL-4 has been shown to have a modest but direct inhibitory effect on the growth of tumor cells of hematopoietic and nonhematopoietic origin in vitro and in vivo , including those derived from human melanoma, non-Hodgkin’s malignant B-lymphoma, and colon, renal, gastric, and breast carcinoma [ 43 – 47 ]. IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine.…”

Serum interleukin‐6 (IL‐6) and interleukin‐4 (IL‐4) in patients with multiple myeloma (MM)

“…IL-6 is an essential growth factor for myeloma cells and increased IL-6 serum levels have been correlated with poor prognosis . IL-4 was shown to have an antitumour effect on several B haematological malignancies including multiple myeloma (Defrance et al, 1992;Taylor et al, 1990). In the present study we examined whether serum levels of IL-6 and IL-4 in patients with MM can be correlated with prognosis.…”