Appearance of neuropeptides in ascitic fluid after peritoneal therapy with interleukin-2 and lymphokine-activated killer cells for intraabdominal malignancy

Abstract

Administration of intravenous interleukin-2 (IL-2), followed by intraperitoneal IL-2 and autologous lymphokine-activated killer (LAK) cells to six patients with colonic, ovarian, or endometrial carcinoma restricted to peritoneal spread increased significantly the ascitic fluid concentrations of the neuropeptides substance P (SP) and calcitonin-gene related peptide (CGRP). After intravenous IL-2 alone, the level of SP rose 10- to 140-fold, without a change in that of CGRP. Intraperitoneal IL-2 and LAK cells led to elevations in the concentrations of SP and CGRP to respective maximal means of 319 and 175 pM after 8 hr, which were maintained for 24-48 hr without alterations in the levels of vasoactive intestinal peptide or somatostatin. SP and CGRP from peritoneal fluid were chromatographically indistinguishable from synthetic neuropeptides. The increases in concentrations of SP and CGRP after IL-2 and LAK-cell therapy are the first demonstration of a neural response to a human cellular immunological reaction. The time course and magnitude of the neuropeptide response suggest a role in the vascular side effects of this form of treatment.