In vivo cytokine production and recombinant interleukin 2 immunotherapy: an insight into the possible mechanisms underlying clinical responses.
Recombinant interleukin 2 (rIL-2), when given to patients with advanced malignant disease, induces a limited beneficial effect, with only 20-30% of patients with solid tumours responding. This present study has identified those patients with advanced colorectal cancer most likely to respond to rIL-2 therapy, by analysis of serum cytokine levels, prior to and during rIL-2 treatment, documented in responders and non-responders. Responders were found to have significantly lower pretreatment serum IL-6 and soluble IL-2 receptor levels (sIL-2R) than non-responders (P < 0.01 and P < 0.05 respectively). During rIL-2 infusion, responders developed high circulating levels of IL-6 and had low constant levels of prostaglandin E2 (PGE2). Non-responders failed to produce IL-6 and demonstrated elevated serum concentrations of PGE2, during infusions of rIL-2. Thus, an enhanced ongoing IL-6 and sIL-2R response, prior to therapy, was detrimental to subsequent treatment with rIL-2. Differential production and/or release of cytokines and prostaglandins, during therapy, further determined the likelihood of response to rIL-2.
Deehan
D J
DJ
Department of Surgery, University of Aberdeen, Scotland, UK.
Heys
S D
SD
Simpson
W G
WG
Broom
J
J
Franks
C
C
Eremin
O
O
D015415:Biomarkers / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000097:blood*; D015232:Dinoprostone / Q000097:blood; D006801:Humans; D007167:Immunotherapy; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood*; D009367:Neoplasm Staging; D011379:Prognosis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D015415:Biomarkers; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D015232:Dinoprostone