All-trans-retinoic acid and polyriboinosinic : polyribocytidylic acid in combination potentiate specific antibody production and cell-mediated immunity.
Retinoic acid (RA), an active metabolite of vitamin A, may synergize with interferons (IFN) to evoke a heightened immune response, suggesting combination therapy as a promising treatment for various cancers. Recently, we demonstrated a strong synergism between RA and polyriboinosinic : polyribocytidylic acid (PIC), an inducer of IFN, on antibody production in immunocompromised vitamin A-deficient animals. In the present study, we examined whether this combination could potentiate T-cell-dependent antibody production in non-immunocompromised rats. Forty male Lewis rats were treated with 100 microg all-trans-RA, 20 microg PIC, or the combination in either an 11-d study to evaluate antibody production, changes in lymphocyte populations, and cell proliferation, or a 21-hr study to evaluate early changes in lymphocyte populations and gene expression. The combination of RA + PIC significantly potentiated anti-tetanus IgG levels (P < 0.002). Similarly, this combination also increased the numbers of B cells and major histocompatibility complex (MHC) class II+ cells in spleen and lymph nodes, and natural killer (NK) cells in spleen and blood (P < 0.05). RA + PIC-treated rats had significantly higher levels of interleukin (IL)-10, IL-12, and signal transducer and activator of transcription-1 (STAT-1) mRNA (P < 0.05), and STAT-1 protein (P < 0.02). Treatments administered in vivo significantly modulated T-cell proliferation to anti-CD3/phorbol myristyl acetate + IFN-alpha ex vivo. These changes in antibody production, cell distribution, cytokine gene expression, and T-cell proliferation suggest that the combination of RA + PIC stimulates humoral and cell-mediated immunity, and deserves further testing in models of cancer chemoprevention in vivo.
DeCicco
K L
KL
The Graduate Program in Nutrition, The Pennsylvania State University, University Park, PA 16802, USA.
Youngdahl
J D
JD
Ross
A C
AC
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000954:Antigens, Surface / Q000378:metabolism; D002266:Carboxymethylcellulose Sodium / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis; D016130:Immunophenotyping; D007369:Interferon Inducers / Q000494:pharmacology; D008297:Male; D011070:Poly I-C / Q000494:pharmacology*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*; D014212:Tretinoin / Q000494:pharmacology*
D000907:Antibodies, Bacterial; D000954:Antigens, Surface; D016207:Cytokines; D007074:Immunoglobulin G; D007369:Interferon Inducers; D012333:RNA, Messenger; D013745:Tetanus Toxoid; D011107:Polylysine; D014212:Tretinoin; C019531:poly ICLC; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C