Gallium nitrate suppresses lupus in MRL/lpr mice.
Gallium (Ga) nitrate, a drug which prevents a variety of experimental autoimmune diseases, was investigated in a murine model of systemic lupus erythematosus (SLE). In one experiment, female MRL/Mp lpr/lpr (MRL/lpr) mice were randomized into 2 groups of 6: 1) vehicle (trisodium citrate) and 2) Ga. Subcutaneous injections began at 3 weeks of age and continued weekly until the mice were euthanized a week after the thirteenth injection. The loading dose of Ga (calculated as elemental Ga) was 45 mg/kg, followed by 15 mg/kg/week. In another experiment (n = 18) with 3 males and 3 females per group, mice received 1) vehicle, 2) Ga x 1 (one 45 mg/kg dose), and 3) Ga x 13. In the experiment with 12 mice, axillary lymph nodes from Ga-treated mice were significantly smaller than those from vehicle-treated mice (91+/-42 and 360+/-358 mg respectively, mean+/-SD), and spleens as well as lymph nodes from the former showed significantly less lymphoid infiltrate. In the experiment with 18 mice, prescapular lymph nodes weighed 312+/-98, 217+/-52, and 42+/-34 mg, and spleens weighed 732+/-492, 409+/-164, and 192+/-93 mg in the groups which received vehicle, Ga x 1, and Ga x 13 respectively. Control mice had significantly more lymphoid infiltrates in the lungs, spleen, and lymph nodes and, unlike Ga x 13 mice, exhibited glomerulitis and renal vasculitis. Within groups, females developed more severe disease than males. The Ga x 13 group had increased percentages of CD4-bearing and CD8-bearing lymphocytes in lymph nodes and increased CD4-bearing lymphocytes in the spleen, with an increased proliferative response to mitogen stimulation in vitro in lymph nodes, although not in the spleen. The Ga x 13 group also gained less weight and developed osteosclerosis. Although preliminary, our findings suggest that clinical trials with Ga in SLE are merited.
Apseloff
G
G
Department of Pharmacology, College of Medicine, The Ohio State University, Columbus 43210-1239, USA.
Hackshaw
K V
KV
Whitacre
C
C
Weisbrode
S E
SE
Gerber
N
N
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D002455:Cell Division; D005260:Female; D005708:Gallium / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008198:Lymph Nodes / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009929:Organ Size; D010012:Osteogenesis; D011897:Random Allocation; D013154:Spleen / Q000473:pathology; D013977:Tibia / Q000473:pathology
D000974:Antibodies, Antinuclear; D007166:Immunosuppressive Agents; D005708:Gallium; C027235:gallium nitrate