Effects of administration of a monoclonal antibody against mouse tumor necrosis factor alpha during pregnancy and lactation on the pre- and postnatal development of the mouse immune system.
Monoclonal antibodies directed against tumor necrosis factor alpha (TNFalpha) are currently employed in the treatment of various immune-mediated diseases. These studies were designed to evaluate potential effects of anti-TNFalpha treatment in mice during pregnancy and lactation on the development of the immune system in the F1 generation. Pregnant CD-1 mice were treated with vehicle or with 10 or 40 mg/kg of an anti-mouse TNFalpha monoclonal antibody (mAb) (cV1q) on days 6, 12, and 18 of gestation and on days 3, 9, and 15 of lactation. Evaluation of immune system functionality was conducted in F1 generation mice at 11 weeks of age. Immune function was evaluated by splenocyte phenotyping, immunoglobulin M (IgM) antibody response to sheep red blood cells (SRBCs), spleen cell proliferative response to anti-CD3, and natural killer cell activity. Treatment of pregnant mice with cV1q produced no adverse effects in the dams and no adverse effects in the F1 generation. In general, the functioning of the immune system of the F1 generation did not appear to be adversely affected following exposure to cV1q in utero and during lactation. The only statistically significant change was a slight (approximately 20%) reduction in the spleen cell expansion in response to SRBC immunization in the female F1 mice from the 40 mg/kg cV1q treatment group. In conclusion, administration of a monoclonal antibody against mouse TNFalpha during pregnancy and lactation had little or no effect on selected immune parameters in mice, with only a possible minor attenuation of spleen cell response to immunization noted in the female F1 generation at 11 weeks of age.
Martin
Pauline L
PL
Department of Toxicology and Investigational Pharmacology, Centocor Research and Development, Inc., 145 King of Prussia Road, Radnor, PA 19087, USA. pmarti27@cntus.jnj.com
Cornacoff
Joel B
JB
Treacy
George
G
Eirikas
Edward
E
Marini
Joseph
J
White
Kimber L
KL
Peachee
Vanessa
V
Hoberman
Alan
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D000917:Antibody Formation; D005260:Female; D007107:Immune System / Q000196:embryology* / Q000254:growth & development*; D007075:Immunoglobulin M / Q000276:immunology; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D007774:Lactation; D008297:Male; D051379:Mice; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D014409:Tumor Necrosis Factor-alpha