THE RELEASE OF INTERLEUKIN-8 DURING INTRAVENOUS BOLUS TREATMENT WITH INTERLEUKIN-2

Objective: To study the role that interleukin-8 might play in the acti vation of polymorphonuclear neutrophils during interleukin-2 therapy a nd the relationship of these phenomena to interleukin-2 induced toxici ty. Design: A cohort study with measurements before and after the admi nistration of interleukin-2. Setting: Medical oncology department of a large teaching hospital. Patients: Fourteen patients with metastatic renal cell carcinoma and 10 with metastatic melanoma being treated in a phase 2 study of the sequential combination of interferon-gamma and interleukin-2. Measurements: Plasma levels of tumour necrosis factor-a lpha, interleukins-6 and 8 and markers of neutrophil activation (neutr ophil elastase and lactoferrin) were measured in patients receiving 5 daily injections of interferon-gamma (100 mu g/m(2)/day) followed by 5 days of interleukin-2 (18 x 10(6) IU/m(2)/day). Main results: Tumour necrosis factor-alpha rose from baseline levels of 32 (range, 12 to 56 ) to 343 (103 to 787) pg/ml 3 hours after interleukin-2 administration returning to baseline values 21 hours later. Interleukins-6 and -8 ro se from baseline levels of 6 (5 to 10) and 75 (35 to 100) to 2151 (152 to 7259) and 1283 (490 to 2500) pg/ml, respectively, at 4 hours after interleukin-2 with both returning to baseline values by 24 hours. Pea k levels of neutrophil elastase and lactoferrin, both markers of neutr ophil activation, occurred 6 hours after interleukin-2 administration. Conclusions: These data indicate that following administration of int erleukin-2 tumour necrosis factor-ct is released followed sequentially by rises in interleukins-6 and -8. It is hypothesised that these even ts result in activation of polymorphonuclear neutrophils. These activa ted neutrophils may play an important role in initiating endothelial c ell damage leading to the haemodynamic toxicity and the capillary leak syndrome which is typically seen following the administration of inte rleukin-2.