Effect of prenatal administration of NSAIDs on the immune response in juvenile and adult rats.
In order to investigate the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the development of rat immunity, indomethacin (IND; 0.25, 0.5, or 1.0 mg/kg/day), acetyl salicylic acid (ASA; 90, 180, or 360 mg/kg/day), or diclofenac sodium salt (DSS; 0.5, 1.0, or 2.0 mg/kg/day) suspended in 0.5% methylcellulose aqueous solution, was orally administered once daily to five pregnant Sprague-Dawley (IGS) rats per group on days 18-21 of gestation. After parturition, the serum IgM and IgG levels, the spleen weight, and the number of spleen cells were measured in 3- and 8-week-old pups. Afterwards, immunophenotyping analysis of splenocytes or peripheral blood lymphocytes and T-dependent antibody response were performed. The number of spleen cells in 3-week-olds increased when 1.0 mg/kg of IND and 180 mg/kg of ASA were administered. Immunophenotyping analysis using flow cytometry (FCM) indicated that the proportion and number of CD45RA(+) cells increased, and the proportion of CD3(-) NKR-P1A(+) cells decreased in males when dosed with IND at 1.0 mg/kg or ASA at 180 mg/kg. The serum anti-KLH IgG antibody titer decreased in the males of the IND 1.0 mg/kg dosing group, the serum levels of anti-KLH IgM, total IgM, and IgG were not changed at all. These changes disappeared in 8-week-old pups. There were no effects on any of the parameters in the 3- and 8-week-olds of the DSS treatment group. These results suggest that IND or ASA administration to dams during late gestation either causes a change in the lymphocyte subsets, or that they suppress the T-dependent antibody response in juvenile males. Both of these changes eventually recover to intact levels later on during development. These results will contribute to the development of a technique for the assessment of developmental immunotoxicity and generate data on the effect of prenatal administration of NSAIDs on the developmental immune system in pups.
Kushima
Kiyoshi
K
Drug Safety Research Laboratories, Astellas Pharma Inc., 1-6 Kashima 2-chome, Yodogawa-ku, Osaka 532-8514, Japan.
Oda
Keiko
K
Sakuma
Shozo
S
Furusawa
Shuichi
S
Fujiwara
Michio
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000276:immunology / Q000494:pharmacology* / Q000633:toxicity; D000917:Antibody Formation / Q000187:drug effects; D001241:Aspirin / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity; D004008:Diclofenac / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006433:Hemocyanins / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood*; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood*; D016130:Immunophenotyping; D007213:Indomethacin / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D018811:Maternal Exposure; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000033:anatomy & histology / Q000187:drug effects / Q000276:immunology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D004008:Diclofenac; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D001241:Aspirin; D007213:Indomethacin