TY - JOUR
T1 - IL-2-based immunotherapy alters circulating neutrophil Fc receptor expression and chemotaxis
AU - Jablons, David
AU - Bolton, Ellen
AU - Mertins, Susan
AU - Rubin, Marc
AU - Pizzo, Philip
AU - Rosenberg, Steven A.
AU - Lotze, Michael T.
PY - 1990/5/1
Y1 - 1990/5/1
N2 - We performed functional assays on polymorphonuclear (PMN) leukocytes from 21 patients with advanced cancers, before, during, and after IL-2 administration. Of these, 19 were treated with high dose bolus IL-2 infusions (105 U/kg every 8 h) and 2 patients received low dose continuous infusions of IL-2 (250 U/kg/h). Five of six patients studied after IL-2 therapy had a decrease in their PMN chemotactic response to FMLP after bolus IL-2 (mean 8 doses) or, after the 4th day of continuous infusion IL-2 (pre-IL-2 values of 82% ± 17% to 45% ± 1% post-IL-2, p2 < 0.004) compared with normal control values. In 8 of 10 patients studied, PMN capacity to oxidize intracellular dichlorofluorescein dye, an indirect measurement of O2- production in response to PMA stimulation, decreased after IL-2 administration (pre-IL-2 mean dichlorofluorescein oxidation (by channel number) 243 ± 128 vs 3-day post-IL-2 87 ± 86, p2 < 0.02). Furthermore, a marked decrease in FcγR III (Leu-11, CD16) expression was observed in 12/13 patients' PMN studied after IL-2 therapy (mean percent of PMN population with positive FcR expression was 81.1 ± 15.4% pre-IL-2 which decreased to 56.0 ± 30.5% post-IL-2, p2 < 0.001). Other PMN surface markers (My4, My7, ICAM-1, LFA1, LFA3, Mac1) did not change significantly. PMN-mediated antibody-dependent cellular cytoxicity did not change after IL-2 therapy (only 4/15 patients demonstrated more than 50% reduction in antibody-dependent cellular cytotoxicity). PMN phagocytosis of Staphylococcus aureus was also not significantly altered by IL-2 administration in six patients studied (pre-IL-2, 99 ± 17% vs 111 ± 28% post-IL-2, p2 > 0.2). We conclude that the systemic administration of IL-2 by intermittent or continuous administration is associated with marked changes in PMN function and cell surface receptor expression. These alterations may contribute to the apparent increased susceptibility to bacterial infection observed in these patients.
AB - We performed functional assays on polymorphonuclear (PMN) leukocytes from 21 patients with advanced cancers, before, during, and after IL-2 administration. Of these, 19 were treated with high dose bolus IL-2 infusions (105 U/kg every 8 h) and 2 patients received low dose continuous infusions of IL-2 (250 U/kg/h). Five of six patients studied after IL-2 therapy had a decrease in their PMN chemotactic response to FMLP after bolus IL-2 (mean 8 doses) or, after the 4th day of continuous infusion IL-2 (pre-IL-2 values of 82% ± 17% to 45% ± 1% post-IL-2, p2 < 0.004) compared with normal control values. In 8 of 10 patients studied, PMN capacity to oxidize intracellular dichlorofluorescein dye, an indirect measurement of O2- production in response to PMA stimulation, decreased after IL-2 administration (pre-IL-2 mean dichlorofluorescein oxidation (by channel number) 243 ± 128 vs 3-day post-IL-2 87 ± 86, p2 < 0.02). Furthermore, a marked decrease in FcγR III (Leu-11, CD16) expression was observed in 12/13 patients' PMN studied after IL-2 therapy (mean percent of PMN population with positive FcR expression was 81.1 ± 15.4% pre-IL-2 which decreased to 56.0 ± 30.5% post-IL-2, p2 < 0.001). Other PMN surface markers (My4, My7, ICAM-1, LFA1, LFA3, Mac1) did not change significantly. PMN-mediated antibody-dependent cellular cytoxicity did not change after IL-2 therapy (only 4/15 patients demonstrated more than 50% reduction in antibody-dependent cellular cytotoxicity). PMN phagocytosis of Staphylococcus aureus was also not significantly altered by IL-2 administration in six patients studied (pre-IL-2, 99 ± 17% vs 111 ± 28% post-IL-2, p2 > 0.2). We conclude that the systemic administration of IL-2 by intermittent or continuous administration is associated with marked changes in PMN function and cell surface receptor expression. These alterations may contribute to the apparent increased susceptibility to bacterial infection observed in these patients.
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M3 - Article
C2 - 2158514
AN - SCOPUS:0025259501
SN - 0022-1767
VL - 144
SP - 3630
EP - 3636
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -