Interleukin-2 enhances biopterins and catecholamines production during adoptive immunotherapy for various cancers

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Abstract
Biopterins production during three different protocols for adoptive immunotherapy for human cancer was investigated. Adoptive immunotherapy treatment with interleukin‐2 (IL‐2) was carried out for 13 patients with malignant melanoma; eight with metastatic renal cell carcinoma; and three with metastatic colon cancer. The authors estimated total biopterins in plasma and lymphokine (IL‐2)‐activated killer cells (LAK) from these patients before and during various treatment phases to determine if increased biopterins production reflects leukocyte activation by IL‐2 or antitumor activity. They noted an increased synthesis of total “biopterins,” i.e., biopterin; 7,8‐dehydrobiopterin; and L‐neopterin, in LAK cells and plasma which correlated with IL‐2 exposure. Mean plasma biopterins were normal (1.2 ± 0.5 ng/ml) before therapy; in contrast, biopterins increased significantly to 3.4 ± 1.9 ng/ml and 3.9 ± 1.9 ng/ml during IL‐2 and IL‐2 + LAK treatment each, respectively. Similar biopterin elevations were noted irrespective of the different adoptive immunotherapy protocols used. Elevated biopterins decreased to normal levels (1.2 ± 0.7 ng/ml) when IL‐2 treatment was omitted. Tumor regression with adoptive immunotherapy did not correlate with increased plasma biopterins. Increased biopterins production was also associated with increase in plasma catecholamine after IL‐2 treatment during adoptive immunotherapy. Conceivably increased biopterins, induced by IL‐2 activation of a leukocyte population, is a cell‐mediated consequence not necessarily serving as a signal for the antitumor effect associated with adoptive immunotherapy.

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