Influence of interferon beta-1a dose frequency on PBMC cytokine secretion and biological effect markers.
Interferon-beta regimens for immune-mediated diseases, such as multiple sclerosis (MS), have not been compared regarding their biological effects. In this randomized, parallel-group, placebo-controlled study, cytokine secretion by mitogen-stimulated PBMCs and serum response markers were assessed in volunteers receiving subcutaneous recombinant IFN beta-1a (Rebif, Ares-Serono) 22 microg once a week (QW), 22 microg three times a week, 66 microg QW, or placebo. The production of IL-1beta, IL-6, IFN-gamma, TNF-alpha and TNF-beta markedly decreased during 24-48 h after each injection, with limited dose-dependency and no evidence of tolerance or effect augmentation over 1 month. IL-10 secretion remained unchanged. The increase in serum beta2-microglobulin, neopterin and 2-5A-synthetase was more sustained. Thus, IFN-beta-induced immunomodulation in vivo strongly depends on the administration schedule, the time-integrated effect being 2-3 times greater when a same weekly dose is divided in three injections.
Rothuizen
L E
LE
Division of Clinical Pharmacology, University Hospital, Lausanne, Switzerland.
Buclin
T
T
Spertini
F
F
Trinchard
I
I
Munafo
A
A
Buchwalder
P A
PA
Ythier
A
A
Biollaz
J
J
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood; D000328:Adult; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005334:Fever / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008297:Male; D019798:Neopterin / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012449:Safety; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000032:analysis
D007155:Immunologic Factors; D007375:Interleukin-1; D015850:Interleukin-6; D008222:Lymphokines; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin; D019798:Neopterin; D016899:Interferon-beta; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase; D000068556:Interferon beta-1a