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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

Centocor Research and Development, Inc., Radnor, Pennsylvania, USA

Kimber L. White, Jr.
Vanessa Peachee

ImmunoTox, Richmond, Virginia, USA

Alan Hoberman

Charles River Laboratories, Horsham, Pennsylvania, USA

Correspondence: Address correspondence to Pauline Martin, PhD, Director of Toxciology, Department of Toxicology and Investigational Pharmacology, Centocor Research and Development, Inc.,145 King of Prussia Road, Radnor, PA 19087, USA. E-mail:pmarti27{at}cntus.jnj.com

Monoclonal antibodies directed against tumor necrosis factor alpha (TNF) are currently employed in the treatment of various immune-mediated diseases. These studies were designed to evaluate potential effects of anti-TNFtreatment 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 TNFmonoclonal 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 (~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 TNFduring 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.

Key Words: Immune System Development • Monoclonal Antibody • Mouse • Tumor Necrosis Alpha

International Journal of Toxicology, Vol. 27, No. 4, 341-347 (2008)
DOI: 10.1080/10915810802368196


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