Pilot study of natural human interleukin-2 in patients with chronic hepatitis B. Immunomodulatory and antiviral effects.
Ten patients with chronic hepatitis B received increasing doses of nIL-2 (30,000 U, 100,000 U, 300,000 U, 1.0 million U) subcutaneously in a phase I trial. Each dose was applied once per week over 3 weeks. Serum samples were taken before and 2, 12, 24, 48 and 72 h after the first application of each dose level. Serum concentrations of interleukin-1 (IL-1), IL-2, IL-6, interferon-alfa (IFN-alpha), IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and GM-CSF as well as the cytokine-dependent serum components neopterin, beta-2-microglobulin (B2M), C-reactive protein (CPR), soluble IL-2-receptor (sIL-2R) and 2'-5'-oligoadenylate synthetase (2-5 OA) were assayed using ELISAs and RIAs. None of the samples tested contained measurable cytokine levels other than IL-2. A low and non-toxic dose of 300,000 U nIL-2 was already biologically active with induction of neopterin, B2M and sIL-2R. Dose-dependent changes peaked 24-48 h after application. The same patients were then enrolled in a phase II trial. Treatment in five of the patients was continued twice per week for 3 months with a biologically active dose of 300,000 U nIL-2 subcutaneously. Two of these patients as well as another five patients from the original group were treated with 1.0 million U nIL-2 subcutaneously, twice weekly for 3 months. Neither a biologically active but non-toxic dose of 300,000 U nIL-2, nor a toxic dose of 1.0 million U resulted in permanent clearance of hepatitis B early antigen (HBeAg).(ABSTRACT TRUNCATED AT 250 WORDS)
Tilg
H
H
Department of Internal Medicine, Innsbruck University, Austria.
Vogel
W
W
Tratkiewicz
J
J
Aulitzky
W E
WE
Herold
M
M
Gruber
M
M
Geissler
D
D
Umlauft
F
F
Judmaier
G
G
Schwulera
U
U
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002908:Chronic Disease; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006509:Hepatitis B / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006801:Humans; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D007376:Interleukin-2 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D010865:Pilot Projects; D011863:Radioimmunoassay; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014779:Virus Replication; D001613:beta 2-Microglobulin / Q000032:analysis
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin; D001708:Biopterins; D019798:Neopterin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002097:C-Reactive Protein; D015088:2',5'-Oligoadenylate Synthetase