IL-2 infusion abrogates humoral immune responses in humans.
Although IL-2 infusion enhances cell-mediated cytotoxicity in patients with neoplastic disease, administration is paradoxically associated with a modest fall in total serum IgG and an increased risk of infection. We now show that the adverse effects of IL-2 infusion on the humoral immune system are substantial. Although IL-2 induces the B cell growth and differentiating factors IL-4 and IL-6, infusion abrogates primary antibody responses entirely and reduces secondary antibody responses 50-fold following antigen challenge. There is no evidence of the generation of cells with suppressive activity on B cells but IL-2 increases the ratio of circulating virgin:memory cells. These results may help to explain the increased rate of bacterial infection in patients receiving IL-2. As IL-2 plays a central role in the generation of an immune response, the finding that it is also sufficiently immunosuppressive to inhibit primary- and secondary-type antibody responses suggests that exploration of the underlying mechanisms may provide insights into immune system homeostasis and may offer new approaches to therapeutic immunosuppression.
Gottlieb
D J
DJ
Department of Haematology, Royal Free Hospital, London, England.
Prentice
H G
HG
Heslop
H E
HE
Bello
C
C
Brenner
M K
MK
D000293:Adolescent; D000328:Adult; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D006433:Hemocyanins / Q000008:administration & dosage; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008974:Mollusca / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000628:therapy; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use
D016207:Cytokines; D007136:Immunoglobulins; D007376:Interleukin-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin