Influence of tumour physico-chemical conditions on interleukin-2-stimulated lymphocyte proliferation.
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.
Loeffler
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DA
E. Walter Albachten Department of Immunology, Michigan Cancer Foundation, Detroit 48201.
Juneau
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PL
Masserant
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D000818:Animals; D002455:Cell Division; D015687:Cell Hypoxia; D005260:Female; D005947:Glucose; D006863:Hydrogen-Ion Concentration; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D007376:Interleukin-2; D005947:Glucose