Soluble Receptors Neutralizing TNF-α and IL-1 Block Stress-Triggered Murine Abortion
| Autor: | Anthony B. Troutt, David A. Clark, Petra C. Arck |
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| Rok vydání: | 1997 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Immunology Substance P Binding Competitive Receptors Tumor Necrosis Factor Pathogenesis Mice chemistry.chemical_compound Pregnancy Stress Physiological Internal medicine medicine Animals Immunology and Allergy Neurotransmitter Receptor Tumor Necrosis Factor-alpha business.industry Decidua Receptors Interleukin-1 Obstetrics and Gynecology Interleukin Abortion Veterinary Endocrinology Cytokine medicine.anatomical_structure Solubility Reproductive Medicine chemistry Mice Inbred DBA Mice Inbred CBA Female Tumor necrosis factor alpha business Interleukin-1 Protein Binding |
| Zdroj: | American Journal of Reproductive Immunology. 37:262-266 |
| ISSN: | 1046-7408 |
| Popis: | PROBLEM In several models of abortion in rodents, the success or failure of the implanted embryos is determined by a balance between pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-2, interleukin-1 (IL-1), and gamma-interferon, and cytokines that counteract the former, such as interleukin-10 and transforming growth factor-beta 2 (TGF-beta 2)-related suppressor factor. Stress can trigger abortions in susceptible strains of mice and is thought to reflect the pathogenesis of some types of miscarriage in human pregnancy. In mice, stress increases levels of the abortogenic cytokine TNF-alpha and decreases the suppressive activity of TGF-beta 2-related factor via a neurotransmitter substance P (SP)-dependent pathway. Evidence for a role of pro-inflammatory cytokines in SP-mediated abortions in vivo is indirect. METHODS Direct evidence for a role of IL-1 and TNF-alpha in stress-triggered abortions was sought by injecting pregnant female mice with soluble receptors neutralizing TNF-alpha (rhuTNFR:Fc) or IL-1 (rmIL-IR) beginning 1 day after implantation and prior to stress. RESULTS The stress-triggered abortion rate was reduced by 68% when either TNF-alpha or IL-1 antagonists were injected. The stress-triggered decreased TGF-beta 2-like suppressive activity in the maternal uterine decidua was not restored by injection of either antagonist; indeed the soluble IL-1 receptor significantly reduced suppressive activity in unstressed control mice, and soluble TNF-alpha receptor had a lesser effect. CONCLUSIONS Both IL-1 and TNF-alpha play a role in the pathogenesis of stress-triggered abortions, and may induce a compensatory physiological increase in suppressive activity in normal pregnancy counteracting pro-inflammatory cytokines. |
| Databáze: | OpenAIRE |
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