INCREASED SYSTEMIC, BUT NOT REGIONAL, NEOPTERIN PRODUCTION FOLLOWING INTRAPERITONEAL ADMINISTRATION OF INTERLEUKIN-2 AND LACK OF EFFECT OF PTERINS UPON LYMPHOKINE-ACTIVATED KILLER-CELL PHENOMENON

Circulating neopterin is derived from monocytes and/or macrophages tha t produce it upon stimulation by interferon-gamma released from activa ted T cells. Neopterin production has been proposed as a marker of bio logical response in the clinical administration of a number of cytokin es. Changes in neopterin production as indicated by urinary neopterin excretion were studied in four patients with ovarian carcinoma receivi ng intraperitoneal interleukin-2 and lymphokine-activated killer cells . Neopterin production increased approximately threefold during treatm ent with interleukin-2 at doses which represent or exceed the maximum tolerated dose by this route of administration. Increased neopterin ap parently was derived from systemic, not regional, tissues. The physiol ogic role(s) of pterins in immune responses is uncertain. In an in vit ro system, the presence of neopterin or tetrahydrobiopterin or the pte rin synthesis inhibitor, N-acetyl serotonin, did not modulate cytotoxi c effects of lymphokine-activated killer cells.