Interleukin-2 enhances biopterins and catecholamines production during adoptive immunotherapy for various cancers.
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.
Baker
H
H
Department of Preventive Medicine, University of Medicine and Dentistry, New Jersey Medical School, Newark 07107.
Marcus
S L
SL
Frank
O
O
Petrylak
D P
DP
DeAngelis
B
B
Dutcher
J P
JP
Wiernik
P H
PH
D000328:Adult; D001708:Biopterins / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000628:therapy; D002395:Catecholamines / Q000096:biosynthesis*; D003110:Colonic Neoplasms / Q000628:therapy; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000628:therapy; D007937:Leukapheresis; D008297:Male; D008545:Melanoma / Q000628:therapy; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D009638:Norepinephrine / Q000097:blood; D012074:Remission Induction
D002395:Catecholamines; D007376:Interleukin-2; D001708:Biopterins; D009638:Norepinephrine