Influence of tumour physico-chemical conditions on interleukin-2-stimulated lymphocyte proliferation

Abstract

The proliferative response of murine lymphocytes to interleukin-2 (IL-2) was examined under physico-chemical conditions present in solid tumours, namely low oxygen and glucose concentrations and acidic pH. Lymphocytes were cultured for four days in 30 U ml-1 IL-2 to simulate serum IL-2 concentrations attainable with high-dose systemic IL-2 therapy. Lymphocyte proliferation was significantly (P < 0.05) reduced by low oxygen concentrations (both anoxia [0% O2] and hypoxia [10%, low glucose (6 mg dl-1), or acidic pH (6.7 or 6.4). Moderate glucose concentration (32 mg dl-1), or neutral pH (7.0) did not impair proliferation. This study indicates that impairment of lymphocyte proliferation by tumour physico-chemical conditions may be a factor in the relatively poor success rate of IL-2/LAK cell immunotherapy.