The effect of linomide, an immunoregulator in experimental autoimmune diseases, on humoral antibody responses in mice.
Linomide (quinoline-3-carboxamide), a well tolerated, orally administered compound was recently shown to be effective in the prevention and treatment of several autoimmune diseases in experimental animal models. We have investigated its effect on specific humoral immune responses directed to T-cell-dependent soluble or particulate antigens and to a T cell-independent antigen in several mouse strains. Linomide administered after antigen priming did not affect primary and secondary antibody responses directed to T-cell particulate antigens (SRBC) or soluble antigens given with or without complete Freund's Adjuvant (CFA). Linomide treatment given prior to antigen priming did not affect the antibody response to a soluble antigen (TNP-KLH) given with an adjuvant. In contrast, dose-dependent down regulation of primary antibody responses was observed when T cell-dependent (BSA-dextran) or T-cell-independent (TNP-Ficoll) antigens were administered in an immunogenic form without adjuvant after starting Linomide treatment. The primary anti-SRBC antibody response was also suppressed by high dose Linomide given prior to immunization although normal secondary responses were retained. It is worth noting that no immunosuppressive effects on antibody responses were found at low dose ranges which effectively reversed T cell dependent autoimmune manifestation.
Morecki
S
S
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Nabet
C
C
Falk
P
P
Fridkis-Hareli
M
M
Pecht
I
I
Mond
J J
JJ
Slavin
S
S
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D017951:Antigen Presentation / Q000187:drug effects; D000955:Antigens, T-Independent / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D003911:Dextrans / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D004334:Drug Administration Schedule; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D005260:Female; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D005620:Freund's Adjuvant; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D006912:Hydroxyquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D007114:Immunization; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D004676:Myelin Basic Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000276:immunology; D012995:Solubility; D014301:Trinitrobenzenes / Q000276:immunology
D000955:Antigens, T-Independent; D001323:Autoantibodies; D001324:Autoantigens; D003911:Dextrans; D006241:Haptens; D006912:Hydroxyquinolines; D007155:Immunologic Factors; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C020529:TNP-ficoll; D014301:Trinitrobenzenes; C043578:bovine serum albumin-dextran conjugate; C407155:myelin basic protein 84-102; C054401:trinitrophenyl keyhole limpet hemocyanin; D005362:Ficoll; D012710:Serum Albumin, Bovine; C045282:roquinimex; D005620:Freund's Adjuvant; D006433:Hemocyanins