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 advance d 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, pr ior to and during rIL-2 treatment, documented in responders and non-re sponders. Responders were found to have significantly lower pretreatme nt serum IL-6 and soluble IL-2 receptor levels (sIL-2R) than non-respo nders (P<0.01 and P<0.05 respectively). During rIL-2 infusion, respond ers developed high circulating levels of IL-6 and had low constant lev els of prostaglandin E(2) (PGE(2)). Non-responders failed to produce I L-6 and demonstrated elevated serum concentrations of PGE(2), during i nfusions 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 prostaglandin s, during therapy, further determined the likelihood of response to rI L-2.