title: The effects of interleukin-6 signal blockade on fertility, embryo-fetal development, and immunization in vivo.
abstract: Possible effects of interleukin-6 (IL-6) on reproductive performance, embryonal development, parturition, and postnatal development have been suggested based on protein/mRNA expression level of IL-6 in related organs, but less is known about functions of IL-6 signals in these areas. Following two different approaches have been employed to investigate the role of IL-6 signals in fertility and pre-/postnatal development: administration of a rat anti-mouse IL-6 receptor antibody, MR16-1, to mice as a neutralizing antibody system, and B6.129S2-Il6(tm1Kopf)/J (IL-6 knockout [KO]) mice as a KO system. By intravenously dosing 50 mg/kg of MR16-1 every 3 days, animals in male and female fertility studies and dams in a pre-/postnatal development study exhibited plasma MR16-1 concentrations much higher than the effective plasma concentration, indicating that MR16-1 exposure was sufficient to completely block IL-6 signals. The concentration of MR16-1 in the plasma of fetuses exceeded that in the plasma of pregnant animals, and MR16-1 concentration in milk was about one-fourth of that in plasma. Both the transient IL-6 signal blockade by MR16-1, and the constitutive IL-6 signal inhibition using IL-6 KO mice in a combined fertility and pre-/postnatal development study, revealed no biologically important effects on fertility, early embryonic development to implantation, or pre-/postnatal development, including IgG/IgM production by keyhole limpet hemocyanin sensitization. These results indicate that IL-6 signals have no unique, noncompensable roles in reproduction and development in the whole body system, although contributions of IL-6 in the signaling network appear to exist, as suggested by previously published investigations.
authors: Fuji Gotemba Research Labs, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan. sakuraitky@chugai-pharm.co.jp
authors: Takayuki
authors: T
authors: Sakurai
authors: Ryo
authors: R
authors: Takai
authors: Heinrich
authors: H
authors: Bürgin
authors: Kana
authors: K
authors: Ishihara
authors: Yuichiro
authors: Y
authors: Sakamoto
authors: Jun
authors: J
authors: Amano
authors: Yoshinobu
authors: Y
authors: Higuchi
authors: Shuichi
authors: S
authors: Chiba
authors: Thomas
authors: T
authors: Singer
authors: Akinori
authors: A
authors: Kawamura
authors: Masami
authors: M
authors: Suzuki
authors: Lutz
authors: L
authors: Müller
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D000915:Antibody Affinity / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects; D003433:Crosses, Genetic; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005333:Fetus / Q000187:drug effects* / Q000196:embryology*; D007114:Immunization; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000172:deficiency / Q000378:metabolism; D007774:Lactation; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D008892:Milk / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D012018:Reflex / Q000187:drug effects; D000685:Serum Amyloid A Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000093242:Interleukin-6 Inhibitors
chemical_list: D057134:Antibodies, Neutralizing; D015850:Interleukin-6; D000685:Serum Amyloid A Protein; D000093242:Interleukin-6 Inhibitors