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Roberto Romero - One of the best experts on this subject based on the ideXlab platform.
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The natural Interleukin-1 receptor antagonist in tem and preterm parturition
American Journal of Obstetrics and Gynecology, 1992Co-Authors: Roberto Romero, Francisco Brandt, Waldo Sepulveda, Charles A Dinarello, Moshe Mazor, David B. Cotton, Murray D. MitchellAbstract:Abstract OBJECTIVE : Interleukin-1 has been implicated in the mechanisms responsible for preterm labor in the setting of infection. The Interleukin-1 receptor antagonist is a new member of the Interleukin-1 gene family that inhibits the biologic effects of Interleukin-1 by blocking its receptors. Reduction of Interleukin-1-induced prostaglandin production by intrauterine tissues may have potential value in the treatment of preterm labor associated with infection. The purpose of these studies was (1) to determine Interleukin-1 receptor antagonist levels in the amniotic fluid of women with term and preterm labor (with and without infection) and (2) to study the effects of Interleukin-1 receptor antagonist on Interleukin-1-induced prostaglandin biosynthesis by human amnion and chorion. STUDY DESIGN : Amniotic fluid was obtained from women in the midtrimester of pregnancy ( n = 20), atterm pregnancy (with and without labor, n = 69), and in preterm labor ( n = 47). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas . Interleukin-1α, Interleukin-1β, and Interleukin-1 receptor antagonist concentrations were measured by immunoassays previously validated for human amniotic fluid. The effect of Interleukin-1 receptor antagonist on Interleukin-1-induced prostaglandin production by amnion and chorion was studied with primary cultures. Cells were incubated with Interleukin-1 receptor antagonist and Interleukin-1α or Interleukin-1β for 16 hours. Prostaglandin E 2 released into the media was assayed by immunoassay. RESULTS : (1) Interleukin-1 receptor antagonist was present in all amniotic fluid samples; (2) amniotic fluid contains the highest Interleukin-1 receptor antagonist concentrations detected in any biologic fluid to date; (3) amniotic fluid Interleukin-1 receptor antagonist concentrations were not increased in women with preterm labor and intraamniotic infection in spite of dramatically elevated concentrations of Interleukin-1∝ and Interleukin-1β in the same fluid (median 22 ng/ml and range 0.16 to 70 for preterm labor with negative amniotic fluid culture vs median 30 ng/ml and range 6 to 70 for preterm labor with positive amniotic fluid culture; p > 0.05); (4) Interleukin-1 receptor antagonist reduced Interleukin-1β-induced prostaglandin E 2 production by amnion and chorion in a dose-dependent manner; (5) Interleukin-1 receptor antagonist by itself did not stimulate prostaglandin E 2 release by amnion and chorion when used in concentrations ranging from 0.1 to 1000 ng/ml. CONCLUSIONS : (1) Interleukin-1 receptor antagonist is a physiologic component of amniotic fluid; (2) therelease of Interleukin-1α and Interleukin-1β into the amniotic fluid in women with preterm labor is not associated with an increase in Interleukin-1 receptor antagonist levels in amniotic fluid; (3) Interleukin-1 receptor antagonist reduces Interleukin-1-induced prostaglandin production by amnion and chorion; (4) exogenous anticytokine agents may be of value in the treatment of preterm labor. (Am J Obstet Gynecol 1992;167:863–72.)
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The natural Interleukin-1 receptor antagonist prevents Interleukin-1-induced preterm delivery in mice.
American journal of obstetrics and gynecology, 1992Co-Authors: Roberto Romero, B TartakovskyAbstract:Interleukin-1 has been implicated in the mechanisms responsible for preterm parturition in the setting of intrauterine infection. This cytokine is produced by human decidua, stimulates prostaglandin production by intrauterine tissues, and induces preterm parturition in mice. The purpose of this study was to determine whether pretreatment with the natural Interleukin-1 receptor antagonist can block Interleukin-1-induced preterm parturition in mice. Balb/CJ female mice impregnated by B6D2 F-1 male mice were randomly allocated to one of the following treatment groups: (1) saline solution (n = 15), (2) human recombinant Interleukin-1 alpha or human recombinant Interleukin-1 beta (n = 12), (3) human recombinant Interleukin-1 receptor antagonist (n = 13), and (4) human recombinant Interleukin-1 receptor antagonist plus human recombinant Interleukin-1 (n = 24). An Interleukin-1 dose of 10 micrograms per mouse induced preterm parturition in all cases. Pretreatment with Interleukin-1 receptor antagonist (dose 1 mg per animal) prevented Interleukin-1-induced preterm parturition. Interleukin-1 receptor antagonist administration was not associated with demonstrable side effects including behavioral changes, vaginal bleeding, duration of pregnancy, and pregnancy outcome. Our results suggest that Interleukin-1-induced preterm delivery in mice is mediated by the Interleukin-1 receptor.
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The natural Interleukin-1 receptor antagonist in term and preterm parturition.
American journal of obstetrics and gynecology, 1992Co-Authors: Roberto Romero, Francisco Brandt, Waldo Sepulveda, Charles A Dinarello, Moshe Mazor, David B. Cotton, Murray D. MitchellAbstract:Interleukin-1 has been implicated in the mechanisms responsible for preterm labor in the setting of infection. The Interleukin-1 receptor antagonist is a new member of the Interleukin-1 gene family that inhibits the biologic effects of Interleukin-1 by blocking its receptors. Reduction of Interleukin-1-induced prostaglandin production by intrauterine tissues may have potential value in the treatment of preterm labor associated with infection. The purpose of these studies was (1) to determine Interleukin-1 receptor antagonist levels in the amniotic fluid of women with term and preterm labor (with and without infection) and (2) to study the effects of Interleukin-1 receptor antagonist on Interleukin-1-induced prostaglandin biosynthesis by human amnion and chorion. Amniotic fluid was obtained from women in the midtrimester of pregnancy (n = 20), at term pregnancy (with and without labor, n = 69), and in preterm labor (n = 47). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Interleukin-1 alpha, Interleukin-1 beta, and Interleukin-1 receptor antagonist concentrations were measured by immunoassays previously validated for human amniotic fluid. The effect of Interleukin-1 receptor antagonist on Interleukin-1-induced prostaglandin production by amnion and chorion was studied with primary cultures. Cells were incubated with Interleukin-1 receptor antagonist and Interleukin-1 alpha or Interleukin-1 beta for 16 hours. Prostaglandin E2 released into the media was assayed by immunoassay. (1) Interleukin-1 receptor antagonist was present in all amniotic fluid samples; (2) amniotic fluid contains the highest Interleukin-1 receptor antagonist concentrations detected in any biologic fluid to date; (3) amniotic fluid Interleukin-1 receptor antagonist concentrations were not increased in women with preterm labor and intraamniotic infection in spite of dramatically elevated concentrations of Interleukin-1 alpha and Interleukin-1 beta in the same fluid (median 22 ng/ml and range 0.16 to 70 for preterm labor with negative amniotic fluid culture vs median 30 ng/ml and range 6 to 70 for preterm labor with positive amniotic fluid culture; p > 0.05); (4) Interleukin-1 receptor antagonist reduced Interleukin-1 beta-induced prostaglandin E2 production by amnion and chorion in a dose-dependent manner; (5) Interleukin-1 receptor antagonist by itself did not stimulate prostaglandin E2 release by amnion and chorion when used in concentrations ranging from 0.1 to 1000 ng/ml. (1) Interleukin-1 receptor antagonist is a physiologic component of amniotic fluid; (2) the release of Interleukin-1 alpha and Interleukin-1 beta into the amniotic fluid in women with preterm labor is not associated with an increase in Interleukin-1 receptor antagonist levels in amniotic fluid; (3) Interleukin-1 receptor antagonist reduces Interleukin-1-induced prostaglandin production by amnion and chorion; (4) exogenous anticytokine agents may be of value in the treatment of preterm labor.
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Systemic administration of Interleukin-1 induces preterm parturition in mice
American Journal of Obstetrics and Gynecology, 1991Co-Authors: Roberto Romero, Moshe Mazor, Boris TartakovskyAbstract:Interleukin-1 has been postulated as a signal for the initiation of preterm labor and delivery. Interleukin-1 is produced by human decidua, stimulates prostaglandin production by intrauterine tissues, and is present in the amniotic fluid of women with preterm labor and intraamniotic infection. The purpose of these studies was to determine whether Interleukin-1 could induce parturition in an animal species. Timed-pregnant C3H/HeJ inbred mice (n = 24) (genetically endotoxin resistant) were randomized to receive either recombinant human Interleukin-1 or sterile phosphate-buffered saline solution between days 15 and 17 of gestation (normal length of pregnancy, 20 to 21 days). Three consecutive subcutaneous injections of Interleukin-1 or phosphate-buffered saline solution were administered within 6 hours. Examinations of the animals were performed by blinded observers. Parturition occurred within 24 hours in all of the Interleukin-1-treated mice and in none of the control group. Vaginal bleeding was first noted 4 hours after the first Interleukin-1 injection, and delivery began within 12 hours after the last Interleukin-1 injection. Premature delivery occurred in all Interleukin-1-injected mice. Laparotomy revealed that there were no remaining fetuses in utero. All mice in the control group delivered spontaneously between days 20 and 22. We conclude that systemic administration of Interleukin-1 induces preterm labor and delivery in mice.
Charles A Dinarello - One of the best experts on this subject based on the ideXlab platform.
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Treating Life-Threatening Myocarditis by Blocking Interleukin-1
Critical care medicine, 2016Co-Authors: Giulio Cavalli, Charles A Dinarello, Federico Pappalardo, Antonio Mangieri, Lorenzo Dagna, Moreno TresoldiAbstract:Objective:Treatment of viral fulminant myocarditis relies on life support measures. Based on studies pointing to a role for the proinflammatory cytokine Interleukin-1 in myocardial inflammation and contractile dysfunction, we treated a patient with fulminant viral myocarditis with the Interleukin-1
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The role of the Interleukin-1-receptor antagonist in blocking inflammation mediated by Interleukin-1.
The New England journal of medicine, 2000Co-Authors: Charles A DinarelloAbstract:Approaches involving the blockade of inflammatory cytokines such as Interleukin-1 and tumor necrosis factor α (TNF-α) are entering mainstream clinical medicine: antibodies against TNF-α and soluble...
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Blocking Interleukin-1 receptors.
International journal of clinical & laboratory research, 1994Co-Authors: Charles A DinarelloAbstract:During inflammation, injury, immunological challenge or infection, Interleukin-1 appears to mediate, in part, the pathogenesis, of disease. Most studies on Interleukin-1 are derived from experiments in which bacterial products, such as endotoxins from Gram-negative bacteria or exotoxins from Gram-positive organisms, are used to stimulate macrophagic cells. In general, several cytokines are induced by microbes to their products. Although cytokines are thought to play a role in the outcome of disease, only a few have been directly implicated as mediators of the pathogenic mechanisms of the host. Studies on specific inhibition of Interleukin-1 activity have employed Interleukin-1 receptor antagonist, Interleukin-1 receptor blocking antibodies or soluble Interleukin-1 receptors. Experiments in vitro, in animal models of disease and in human subjects have shed considerable light on a critical role for Interleukin-1 in the pathogenesis of disease. This review focuses on Interleukin-1 as a cytokine of strategic importance to the outcome of disease, particularly inflammatory and infectious diseases.
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Interleukin-1 receptor antagonist: an index of dialysis-induced Interleukin-1 production.
Nephron, 1994Co-Authors: Brian J.g. Pereira, Andrew J. King, Matheos E. Falagas, Charles A DinarelloAbstract:Interleukin-1 receptor antagonist (IL-1Ra) is a specific inhibitor of Interleukin-1 (IL-1). It is structurally similar to IL-1 and binds to IL-1 cell surface receptors, but does not transduce a signal. To examine the relationship between the production of IL-1Ra and IL-1, we incubated peripheral blood mononuclear cells (PBMC) with endotoxin (10 ng/ml) and after 24 h measured the total synthesis (intra- and extracellular) of IL-1Ra, IL-lα and IL-1β. PBMC from 25 patients with chronic renal failure were studied. The total synthesis of IL-1Ra closely correlated with that of IL-1β (R = 0.786, p 0.05). These results suggest that in dialysis patients, the endogenous production of IL-1Ra is a ‘footprint’ of IL-1β production and can probably be used as a marker of the level of production of IL-1.
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The Role of Interleukin-1 in Disease
The New England journal of medicine, 1993Co-Authors: Charles A Dinarello, Sheldon M. WolffAbstract:The Interleukin-1 family consists of three structurally related polypeptides. The first two are Interleukin-1α and Interleukin-1β, each of which has a broad spectrum of both beneficial and harmful biologic actions, and the third is Interleukin-1-receptor antagonist, which inhibits the activities of Interleukin-1. Among the properties of the two forms of Interleukin-1 (α and β) is the ability to induce fever, sleep, anorexia, and hypotension. Interleukin-1 stimulates the release of pituitary hormones, increases the synthesis of collagenases, resulting in the destruction of cartilage, and stimulates the production of prostaglandins, leading to a decrease in the pain threshold. Interleukin-1 has also been . . .
Marianne Schultzberg - One of the best experts on this subject based on the ideXlab platform.
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Co-localization of Interleukin-1 receptor type I and Interleukin-1 receptor antagonist with vasopressin in magnocellular neurons of the paraventricular and supraoptic nuclei of the rat hypothalamus.
Neuroscience, 1999Co-Authors: A. Diana, A.-m. Van Dam, Bengt Winblad, Marianne SchultzbergAbstract:Interleukin-1 receptor type I and Interleukin-1 receptor antagonist were found in magnocellular neurons of the paraventricular and supraoptic nuclei of the rat hypothalamus by immunohistochemical detection. Double-labelling experiments revealed that both proteins occurred in vasopressin-containing neurons. A similar distribution pattern was observed in a group of vasopressin-positive accessory magnocellular neurons. Axons emanating from the Interleukin-1 receptor type I- and Interleukin-1 receptor antagonist-immunoreactive neuronal cell bodies could be seen within the hypothalamic nuclei, and varicosities expressing Interleukin-1 receptor antagonist immunoreactivity were observed in the internal zone of the median eminence, as well as in the hypothalamo-pituitary projection. The co-localization of Interleukin-1 receptor type I with vasopressin is in agreement with findings that Interleukin-1 has a stimulatory effect on vasopressin synthesis and release. The hypothalamic neurons may serve as a source of Interleukin-1 receptor antagonist to balance the effects of Interleukin-1.
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Interleukin-1 receptor antagonist protein and mRNA in the rat adrenal gland.
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, 1995Co-Authors: Marianne Schultzberg, Stefan B. Svenson, Susanne Tingsborg, Stefan Nobel, Johan Lundkvist, András Simoncsits, Tamas BartfaiAbstract:The occurrence of the endogenous receptor antagonist for the cytokine Interleukin-1 in the rat adrenal gland was analyzed y polymerase chain reaction and by immunohistochemistry using a rabbit polyclonal antiserum. Expression of Interleukin-1 receptor antagonist mRNA was demonstrated in both adrenal medulla and cortex, and a marked increase in the transcription was observed after systemic administration of lipopolysaccharides. Interleukin-1 receptor antagonist immunoreactivity was seen in the adrenal medulla, and the immunofluorescence intensity was stronger in the adrenergic, phenylethanolamine N-methyltransferase-positive cells than in the noradrenergic chromaffin cells. The distribution of Interleukin-1 receptor antagonist protein is complementary to that of Interleukin-1 alpha-like immunoreactivity found in phenylethanolamine N-methyltransferase-negative cells and overlaps with and resembles the distribution of Interleukin-1 beta-immunoreactive material. The expression of the Interleukin-1 receptor antagonist in the adrenal gland complements previous findings of large constitutive pools of Interleukin-1 alpha and Interleukin-1 beta in this neuroendocrine organ and also suggests participation of adrenal Interleukin-1 receptor antagonist in neuroimmune modulation.
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Interleukin-1 immunoreactive nerve fibres in rat joint synovium.
Clinical and experimental rheumatology, 1994Co-Authors: A. Bjurholm, Mahmood Ahmed, S.b. Svenson, Andris Kreicbergs, Marianne SchultzbergAbstract:The occurrence of Interleukin-1 immunoreactive nerves in the synovial membrane of rat knee joints was investigated by immunohistochemistry. Synovial tissue sections from 11 rats consistently showed Interleukin-1 positive nerve fibres. The majority of the fibres appeared in blood vessel walls. However, varicose Interleukin-1 positive fibres were also seen to terminate amidst synoviocytes. The overall distribution resembled that of autonomic fibres previously identified in synovium. Further investigation by double staining disclosed the co-existence of Interleukin-1 and neuropeptide Y in the synovial nerve fibres. It has been suggested that the nervous system is implicated in the pathogenesis of arthritis. Considering the role of the cytokine Interleukin-1 in various immunogenic and inflammatory conditions, it may prove that neuronal Interleukin-1 in the synovial membrane represents a pathway for mediating such effects in joint tissue.
Murray D. Mitchell - One of the best experts on this subject based on the ideXlab platform.
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The natural Interleukin-1 receptor antagonist in tem and preterm parturition
American Journal of Obstetrics and Gynecology, 1992Co-Authors: Roberto Romero, Francisco Brandt, Waldo Sepulveda, Charles A Dinarello, Moshe Mazor, David B. Cotton, Murray D. MitchellAbstract:Abstract OBJECTIVE : Interleukin-1 has been implicated in the mechanisms responsible for preterm labor in the setting of infection. The Interleukin-1 receptor antagonist is a new member of the Interleukin-1 gene family that inhibits the biologic effects of Interleukin-1 by blocking its receptors. Reduction of Interleukin-1-induced prostaglandin production by intrauterine tissues may have potential value in the treatment of preterm labor associated with infection. The purpose of these studies was (1) to determine Interleukin-1 receptor antagonist levels in the amniotic fluid of women with term and preterm labor (with and without infection) and (2) to study the effects of Interleukin-1 receptor antagonist on Interleukin-1-induced prostaglandin biosynthesis by human amnion and chorion. STUDY DESIGN : Amniotic fluid was obtained from women in the midtrimester of pregnancy ( n = 20), atterm pregnancy (with and without labor, n = 69), and in preterm labor ( n = 47). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas . Interleukin-1α, Interleukin-1β, and Interleukin-1 receptor antagonist concentrations were measured by immunoassays previously validated for human amniotic fluid. The effect of Interleukin-1 receptor antagonist on Interleukin-1-induced prostaglandin production by amnion and chorion was studied with primary cultures. Cells were incubated with Interleukin-1 receptor antagonist and Interleukin-1α or Interleukin-1β for 16 hours. Prostaglandin E 2 released into the media was assayed by immunoassay. RESULTS : (1) Interleukin-1 receptor antagonist was present in all amniotic fluid samples; (2) amniotic fluid contains the highest Interleukin-1 receptor antagonist concentrations detected in any biologic fluid to date; (3) amniotic fluid Interleukin-1 receptor antagonist concentrations were not increased in women with preterm labor and intraamniotic infection in spite of dramatically elevated concentrations of Interleukin-1∝ and Interleukin-1β in the same fluid (median 22 ng/ml and range 0.16 to 70 for preterm labor with negative amniotic fluid culture vs median 30 ng/ml and range 6 to 70 for preterm labor with positive amniotic fluid culture; p > 0.05); (4) Interleukin-1 receptor antagonist reduced Interleukin-1β-induced prostaglandin E 2 production by amnion and chorion in a dose-dependent manner; (5) Interleukin-1 receptor antagonist by itself did not stimulate prostaglandin E 2 release by amnion and chorion when used in concentrations ranging from 0.1 to 1000 ng/ml. CONCLUSIONS : (1) Interleukin-1 receptor antagonist is a physiologic component of amniotic fluid; (2) therelease of Interleukin-1α and Interleukin-1β into the amniotic fluid in women with preterm labor is not associated with an increase in Interleukin-1 receptor antagonist levels in amniotic fluid; (3) Interleukin-1 receptor antagonist reduces Interleukin-1-induced prostaglandin production by amnion and chorion; (4) exogenous anticytokine agents may be of value in the treatment of preterm labor. (Am J Obstet Gynecol 1992;167:863–72.)
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The natural Interleukin-1 receptor antagonist in term and preterm parturition.
American journal of obstetrics and gynecology, 1992Co-Authors: Roberto Romero, Francisco Brandt, Waldo Sepulveda, Charles A Dinarello, Moshe Mazor, David B. Cotton, Murray D. MitchellAbstract:Interleukin-1 has been implicated in the mechanisms responsible for preterm labor in the setting of infection. The Interleukin-1 receptor antagonist is a new member of the Interleukin-1 gene family that inhibits the biologic effects of Interleukin-1 by blocking its receptors. Reduction of Interleukin-1-induced prostaglandin production by intrauterine tissues may have potential value in the treatment of preterm labor associated with infection. The purpose of these studies was (1) to determine Interleukin-1 receptor antagonist levels in the amniotic fluid of women with term and preterm labor (with and without infection) and (2) to study the effects of Interleukin-1 receptor antagonist on Interleukin-1-induced prostaglandin biosynthesis by human amnion and chorion. Amniotic fluid was obtained from women in the midtrimester of pregnancy (n = 20), at term pregnancy (with and without labor, n = 69), and in preterm labor (n = 47). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Interleukin-1 alpha, Interleukin-1 beta, and Interleukin-1 receptor antagonist concentrations were measured by immunoassays previously validated for human amniotic fluid. The effect of Interleukin-1 receptor antagonist on Interleukin-1-induced prostaglandin production by amnion and chorion was studied with primary cultures. Cells were incubated with Interleukin-1 receptor antagonist and Interleukin-1 alpha or Interleukin-1 beta for 16 hours. Prostaglandin E2 released into the media was assayed by immunoassay. (1) Interleukin-1 receptor antagonist was present in all amniotic fluid samples; (2) amniotic fluid contains the highest Interleukin-1 receptor antagonist concentrations detected in any biologic fluid to date; (3) amniotic fluid Interleukin-1 receptor antagonist concentrations were not increased in women with preterm labor and intraamniotic infection in spite of dramatically elevated concentrations of Interleukin-1 alpha and Interleukin-1 beta in the same fluid (median 22 ng/ml and range 0.16 to 70 for preterm labor with negative amniotic fluid culture vs median 30 ng/ml and range 6 to 70 for preterm labor with positive amniotic fluid culture; p > 0.05); (4) Interleukin-1 receptor antagonist reduced Interleukin-1 beta-induced prostaglandin E2 production by amnion and chorion in a dose-dependent manner; (5) Interleukin-1 receptor antagonist by itself did not stimulate prostaglandin E2 release by amnion and chorion when used in concentrations ranging from 0.1 to 1000 ng/ml. (1) Interleukin-1 receptor antagonist is a physiologic component of amniotic fluid; (2) the release of Interleukin-1 alpha and Interleukin-1 beta into the amniotic fluid in women with preterm labor is not associated with an increase in Interleukin-1 receptor antagonist levels in amniotic fluid; (3) Interleukin-1 receptor antagonist reduces Interleukin-1-induced prostaglandin production by amnion and chorion; (4) exogenous anticytokine agents may be of value in the treatment of preterm labor.
Moshe Mazor - One of the best experts on this subject based on the ideXlab platform.
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The natural Interleukin-1 receptor antagonist in tem and preterm parturition
American Journal of Obstetrics and Gynecology, 1992Co-Authors: Roberto Romero, Francisco Brandt, Waldo Sepulveda, Charles A Dinarello, Moshe Mazor, David B. Cotton, Murray D. MitchellAbstract:Abstract OBJECTIVE : Interleukin-1 has been implicated in the mechanisms responsible for preterm labor in the setting of infection. The Interleukin-1 receptor antagonist is a new member of the Interleukin-1 gene family that inhibits the biologic effects of Interleukin-1 by blocking its receptors. Reduction of Interleukin-1-induced prostaglandin production by intrauterine tissues may have potential value in the treatment of preterm labor associated with infection. The purpose of these studies was (1) to determine Interleukin-1 receptor antagonist levels in the amniotic fluid of women with term and preterm labor (with and without infection) and (2) to study the effects of Interleukin-1 receptor antagonist on Interleukin-1-induced prostaglandin biosynthesis by human amnion and chorion. STUDY DESIGN : Amniotic fluid was obtained from women in the midtrimester of pregnancy ( n = 20), atterm pregnancy (with and without labor, n = 69), and in preterm labor ( n = 47). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas . Interleukin-1α, Interleukin-1β, and Interleukin-1 receptor antagonist concentrations were measured by immunoassays previously validated for human amniotic fluid. The effect of Interleukin-1 receptor antagonist on Interleukin-1-induced prostaglandin production by amnion and chorion was studied with primary cultures. Cells were incubated with Interleukin-1 receptor antagonist and Interleukin-1α or Interleukin-1β for 16 hours. Prostaglandin E 2 released into the media was assayed by immunoassay. RESULTS : (1) Interleukin-1 receptor antagonist was present in all amniotic fluid samples; (2) amniotic fluid contains the highest Interleukin-1 receptor antagonist concentrations detected in any biologic fluid to date; (3) amniotic fluid Interleukin-1 receptor antagonist concentrations were not increased in women with preterm labor and intraamniotic infection in spite of dramatically elevated concentrations of Interleukin-1∝ and Interleukin-1β in the same fluid (median 22 ng/ml and range 0.16 to 70 for preterm labor with negative amniotic fluid culture vs median 30 ng/ml and range 6 to 70 for preterm labor with positive amniotic fluid culture; p > 0.05); (4) Interleukin-1 receptor antagonist reduced Interleukin-1β-induced prostaglandin E 2 production by amnion and chorion in a dose-dependent manner; (5) Interleukin-1 receptor antagonist by itself did not stimulate prostaglandin E 2 release by amnion and chorion when used in concentrations ranging from 0.1 to 1000 ng/ml. CONCLUSIONS : (1) Interleukin-1 receptor antagonist is a physiologic component of amniotic fluid; (2) therelease of Interleukin-1α and Interleukin-1β into the amniotic fluid in women with preterm labor is not associated with an increase in Interleukin-1 receptor antagonist levels in amniotic fluid; (3) Interleukin-1 receptor antagonist reduces Interleukin-1-induced prostaglandin production by amnion and chorion; (4) exogenous anticytokine agents may be of value in the treatment of preterm labor. (Am J Obstet Gynecol 1992;167:863–72.)
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The natural Interleukin-1 receptor antagonist in term and preterm parturition.
American journal of obstetrics and gynecology, 1992Co-Authors: Roberto Romero, Francisco Brandt, Waldo Sepulveda, Charles A Dinarello, Moshe Mazor, David B. Cotton, Murray D. MitchellAbstract:Interleukin-1 has been implicated in the mechanisms responsible for preterm labor in the setting of infection. The Interleukin-1 receptor antagonist is a new member of the Interleukin-1 gene family that inhibits the biologic effects of Interleukin-1 by blocking its receptors. Reduction of Interleukin-1-induced prostaglandin production by intrauterine tissues may have potential value in the treatment of preterm labor associated with infection. The purpose of these studies was (1) to determine Interleukin-1 receptor antagonist levels in the amniotic fluid of women with term and preterm labor (with and without infection) and (2) to study the effects of Interleukin-1 receptor antagonist on Interleukin-1-induced prostaglandin biosynthesis by human amnion and chorion. Amniotic fluid was obtained from women in the midtrimester of pregnancy (n = 20), at term pregnancy (with and without labor, n = 69), and in preterm labor (n = 47). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Interleukin-1 alpha, Interleukin-1 beta, and Interleukin-1 receptor antagonist concentrations were measured by immunoassays previously validated for human amniotic fluid. The effect of Interleukin-1 receptor antagonist on Interleukin-1-induced prostaglandin production by amnion and chorion was studied with primary cultures. Cells were incubated with Interleukin-1 receptor antagonist and Interleukin-1 alpha or Interleukin-1 beta for 16 hours. Prostaglandin E2 released into the media was assayed by immunoassay. (1) Interleukin-1 receptor antagonist was present in all amniotic fluid samples; (2) amniotic fluid contains the highest Interleukin-1 receptor antagonist concentrations detected in any biologic fluid to date; (3) amniotic fluid Interleukin-1 receptor antagonist concentrations were not increased in women with preterm labor and intraamniotic infection in spite of dramatically elevated concentrations of Interleukin-1 alpha and Interleukin-1 beta in the same fluid (median 22 ng/ml and range 0.16 to 70 for preterm labor with negative amniotic fluid culture vs median 30 ng/ml and range 6 to 70 for preterm labor with positive amniotic fluid culture; p > 0.05); (4) Interleukin-1 receptor antagonist reduced Interleukin-1 beta-induced prostaglandin E2 production by amnion and chorion in a dose-dependent manner; (5) Interleukin-1 receptor antagonist by itself did not stimulate prostaglandin E2 release by amnion and chorion when used in concentrations ranging from 0.1 to 1000 ng/ml. (1) Interleukin-1 receptor antagonist is a physiologic component of amniotic fluid; (2) the release of Interleukin-1 alpha and Interleukin-1 beta into the amniotic fluid in women with preterm labor is not associated with an increase in Interleukin-1 receptor antagonist levels in amniotic fluid; (3) Interleukin-1 receptor antagonist reduces Interleukin-1-induced prostaglandin production by amnion and chorion; (4) exogenous anticytokine agents may be of value in the treatment of preterm labor.
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Systemic administration of Interleukin-1 induces preterm parturition in mice
American Journal of Obstetrics and Gynecology, 1991Co-Authors: Roberto Romero, Moshe Mazor, Boris TartakovskyAbstract:Interleukin-1 has been postulated as a signal for the initiation of preterm labor and delivery. Interleukin-1 is produced by human decidua, stimulates prostaglandin production by intrauterine tissues, and is present in the amniotic fluid of women with preterm labor and intraamniotic infection. The purpose of these studies was to determine whether Interleukin-1 could induce parturition in an animal species. Timed-pregnant C3H/HeJ inbred mice (n = 24) (genetically endotoxin resistant) were randomized to receive either recombinant human Interleukin-1 or sterile phosphate-buffered saline solution between days 15 and 17 of gestation (normal length of pregnancy, 20 to 21 days). Three consecutive subcutaneous injections of Interleukin-1 or phosphate-buffered saline solution were administered within 6 hours. Examinations of the animals were performed by blinded observers. Parturition occurred within 24 hours in all of the Interleukin-1-treated mice and in none of the control group. Vaginal bleeding was first noted 4 hours after the first Interleukin-1 injection, and delivery began within 12 hours after the last Interleukin-1 injection. Premature delivery occurred in all Interleukin-1-injected mice. Laparotomy revealed that there were no remaining fetuses in utero. All mice in the control group delivered spontaneously between days 20 and 22. We conclude that systemic administration of Interleukin-1 induces preterm labor and delivery in mice.