Correlation of serum cytokine and acute phase reactant levels with alterations in weight and serum albumin in patients receiving immunotherapy with recombinant IL-2.
Recombinant IL-2 (rIL-2) has been used alone or in combination with other chemotherapeutic agents to enhance host defences against cancer. Prolonged administration of high doses, required for clinical efficacy, may precipitate serious dose-limiting toxicity. rIL-2-induced 'vascular leak syndrome' leads to hypotension, renal insufficiency, respiratory disturbances and other organ dysfunctions. Serial measurements of serum cytokines and the acute phase protein C-reactive protein (CRP) were performed on nine patients who received high-dose i.v. continuous therapy with rIL-2. The influence of these immunological parameters upon alterations in patients' weight and serum albumin, as indicators of toxicity, was assessed. All patients experienced weight increases during the cycle (3-11% of total body weight). The serum levels of tumour necrosis factor (TNF-alpha) and CRP were highly predictive of alterations in patients' weight (both P < 0.001), while no correlation was found with IL-6 and weight change. Serum albumin fell linearly throughout the infusion cycle, but this showed no correlation with variations in serum levels of IL-6, TNF-alpha, or CRP. The complement components C3 and C4 were significantly reduced at the end of the infusion, suggesting a possible role for this cascade system in mediating these clinical changes. The strong association between serum TNF-alpha and weight change, not previously documented, further supports the hypothesis that TNF-alpha is a key mediator in the pathogenesis of the 'vascular leak syndrome'.
Deehan
D J
DJ
Department of Surgery, University of Aberdeen, UK.
Heys
S D
SD
Simpson
W
W
Herriot
R
R
Broom
J
J
Eremin
O
O
D000209:Acute-Phase Proteins / Q000032:analysis; D001835:Body Weight; D002097:C-Reactive Protein / Q000032:analysis; D002277:Carcinoma / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003165:Complement System Proteins / Q000032:analysis; D016207:Cytokines / Q000097:blood; D006801:Humans; D007167:Immunotherapy; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012709:Serum Albumin / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000209:Acute-Phase Proteins; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D003165:Complement System Proteins; D002097:C-Reactive Protein