Elevated circulating levels of soluble interleukin-1 receptor type II during interleukin-2 immunotherapy.
Interleukin-1 (IL-1) is a critical mediator of inflammation. Two naturally occurring IL-1 antagonists have been described, namely the IL-1 receptor antagonist (IL-1Ra) and the IL-1 receptor type II (IL-1RII). IL-1RII does not transmit a signal upon binding of IL-1, but competes with the signaling of IL-1RI for binding of IL-1. Shedding of IL-1RII yields the soluble IL-1 receptor type II (IL-1sRII) which retains the ability of membrane-bound IL-1RII to bind IL-1beta avidly, but binds IL-1Ra and IL-1alpha with low affinity. In contrast, IL-1sRI retains the ability of membrane-bound IL-1RI to bind IL-1Ra and IL-1alpha with high affinity, but binds IL-1beta poorly. We have previously shown that immunotherapy with IL-2 or IL-6 in cancer patients is associated with a dramatic increase in IL-1Ra plasma levels. In the present study, plasma levels of soluble IL-1 receptors were monitored in healthy individuals and cancer patients. In healthy controls, the mean IL-1sRII level was 4.76 0.16 ng/ml. IL-1sRII levels in cancer patients were comparable to those measured in healthy controls. IL-1sRII levels did not vary during the first 52 hours after initiation of IL-2 therapy, but increased significantly thereafter to reach 9.56 1.16 ng/ml on day 5. In contrast, IL-6 immunotherapy with a 5-day continuous infusion did not trigger an increase in IL-1sRII levels. IL-1sRI levels did not increase during immunotherapy with IL-2 or IL-6. Our results indicate that IL-1sRII, unlike IL-1Ra, remains a modest, natural, anti-inflammatory mechanism triggered by immunotherapy with IL-2, but not with IL-6.
Vannier
E
E
Department of Medicine, Division of Geographic Medicine and Infectious Diseases, New England Medical Center and Tufts University School of Medicine, Boston, MA, USA.
Kaser
A
A
Atkins
M B
MB
Fantuzzi
G
G
Dinarello
C A
CA
Mier
J W
JW
Tilg
H
H
D002292:Carcinoma, Renal Cell / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D017472:Receptors, Interleukin-1 / Q000097:blood*; D053574:Receptors, Interleukin-1 Type II; D012016:Reference Values; D013997:Time Factors
D007376:Interleukin-2; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II