title: Development of antihuman IgG antibodies and hematologic deficits but not clinical abnormalities in C57BL/6 mice after repeated administration of human intravenous immunoglobulin.
abstract: Intravenous immunoglobulin (IvIg) preparations consist of purified human immunoglobulins collected from large numbers of healthy persons and are used to treat autoimmune, immunodeficiency, and inflammatory disorders. Studying the effects of IvIg effects in experimental animal models  might clarify its mechanisms of action in these disorders, but whether 'serum sickness' or other abnormalities occur after repeated IvIg administration to immunocompetent animals is unknown. In the current study, male C57BL/6 mice (8 to 10 wk old; n = 27) received IvIg (1 g/kg IP) weekly  for 6 wk. They were observed for clinical abnormalities, and body weight, temperature, renal function, hematologic parameters, and serum antihuman IgG antibodies were measured before and during treatment. Postmortem evaluations were performed on kidney, spleen, liver, and heart. No clinical  or histologic abnormalities were noted despite a transient increase in BUN. Mean antibody levels to human IgG on days 21 and 43 after IvIg administration were increased by 23-fold compared with pretreatment levels. 88% and 89% of the mice were antibody responders on those days. Unexpectedly,  hemoglobin, hematocrit, and RBC, WBC, lymphocyte, and platelet counts decreased after IvIg administration. These findings suggest that although it does not produce serum sickness, repeated IvIg administration to immunocompetent mice induces a strong humoral immune response and hematologic  deficits of unknown etiology. These factors could cause the effects of IvIg preparations in mouse models of human disease to differ from their effects in the human disorders.
authors.affiliation: Department of Neurology Research, William Beaumont Hospital, Royal Oak, Michigan, USA. DLoeffler@beaumont.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Loeffler
authors.forename: Lynnae M
authors.initials: LM
authors.lastname: Smith
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Klaver
authors.forename: Heather A
authors.initials: HA
authors.lastname: Brzezinski
authors.forename: Essie I
authors.initials: EI
authors.lastname: Morrison
authors.forename: Mary P
authors.initials: MP
authors.lastname: Coffey
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Steficek
authors.forename: Susan S
authors.initials: SS
authors.lastname: Cook
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001835:Body Weight; D004797:Enzyme-Linked Immunosorbent Assay; D006403:Hematologic Tests; D006652:Histological Techniques; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000276:immunology*; D007668:Kidney / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013696:Temperature
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous