Effects of oral administration of interferon-alpha on antibody production in mice with induced tolerance.
In vivo systemic effects and the immunomodulating potential of the oral administration of murine interferon-alpha (IFN-alpha) were investigated through mRNA expression of both IFN-alpha-inducible factors, interferon regulatory factor-1 (IRF-1) and 2,5-adenylate synthetase [2-5(A) synthetase] and 2-5(A) synthetase enzymatic activity in spleen and antibody production. The daily administration of IFN-alpha (0.1, 1, 10, and 100 IU/body) for 1 week augmented IRF-1 and 2-5(A) synthetase mRNA expression levels, as well as 2-5(A) synthetase enzymatic activity in spleen cells but not in cervical lymph nodes. The in vivo immunomodulating potential of the oral administration of IFN-alpha was also evaluated through antibody production in mice with induced tolerance. Ovalbumin (OVA) was administered intraperitoneally (i.p.) to induce systemic antibody production on day 0 when OVA feeding was initiated. The OVA was fed every 2-3 days for a total of 14 doses to suppress serum antibody levels. Oral administration of murine IFN-alpha was initiated on day 0 and was continued for 5 consecutive days weekly for 5 weeks (24 doses). On every sampling date (days 10, 17, 24, and 32), specific antibody levels in the IFN-alpha-administered groups were significantly higher than those in the control (nonadministered) group. This was especially noted in early phases (days 10 and 17) of antibody production when the levels of antibody in serum from the IFN-alpha-administration groups were equivalent to those of the nontolerance group. Altogether, it is suggested that oral use of IFN-alpha can elicit immunomodulating actions (e.g., antibody levels) by affecting the systemic immune system(s).
Takayama
S
S
Fujisaki Institute, Hayashibara Biochemical Labs., Inc., Okayama, Japan.
Iwaki
K
K
Nishida
Y
Y
Tanaka
M
M
Fujii
M
M
Ohashi
K
K
Ikeda
M
M
Kurimoto
M
M
D015088:2',5'-Oligoadenylate Synthetase / Q000187:drug effects; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation; D004268:DNA-Binding Proteins / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D015088:2',5'-Oligoadenylate Synthetase