title: Retinoic acid and polyriboinosinic acid act synergistically to enhance the antibody response to tetanus toxoid during vitamin A deficiency: possible involvement of interleukin-2 receptor-beta, signal transducer and activator of transcription-1, and interferon regulatory factor-1.
abstract: Antibody responses to T cell-dependent antigens are reduced during vitamin A (VA) deficiency and restored by retinoids. To test whether retinoic acid (RA) and polyinosinic:polycytidylic acid (PIC), an inducer of interferons, can increase specific antibody production, VA-deficient rats were treated with all-trans-RA, PIC, or both at the time of primary immunization with tetanus toxoid. VA-deficient rats produced low primary and secondary anti-tetanus IgG responses (P<.001 vs. VA-sufficient controls). Both responses were increased synergistically by RA plus PIC (P<.0001). In VA-deficient spleens, mRNAs were low for interleukin (IL)-2 receptor-beta, interferon regulatory factor-1, and signal transducer and activator of transcription 1. Each, however, was induced by RA plus PIC (P<.0001 vs. controls). Conversely, IL-12 and IL-10 mRNAs were elevated in VA deficiency and were induced by PIC and suppressed by RA. Thus, RA plus PIC appears to be a promising combination for stimulating antigen-specific immunity. Several molecular factors identified here may partially account for the observed enhancement.
authors.affiliation: Department of Nutrition, Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: DeCicco
authors.forename: R
authors.initials: R
authors.lastname: Zolfaghari
authors.forename: N q
authors.initials: Nq
authors.lastname: Li
authors.forename: A C
authors.initials: AC
authors.lastname: Ross
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D004357:Drug Synergism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood*; D050856:Interferon Regulatory Factor-1; D007774:Lactation; D008297:Male; D010750:Phosphoproteins / Q000235:genetics*; D011069:Poly I / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D019707:Receptors, Chemokine / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics*; D023063:Receptors, Interleukin-8B; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D013154:Spleen / Q000187:drug effects / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014802:Vitamin A Deficiency / Q000097:blood / Q000188:drug therapy / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D050856:Interferon Regulatory Factor-1; C494259:Irf1 protein, rat; D010750:Phosphoproteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D023063:Receptors, Interleukin-8B; D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; D013745:Tetanus Toxoid; D015534:Trans-Activators; D014157:Transcription Factors; D011069:Poly I; D014212:Tretinoin