dinoprost and Fever

The actions of prostanoids in various physiological and pathophysiological conditions have been being examined using mice lacking different prostanoid receptors. Prostaglandin (PG) I2 worked not only as a mediator of inflammation but also as an antithrombotic agent. PGF2alpha was found to be an essential inducer of labor. Several important actions of PGE2 are exerted via each of the four PGE2 receptor subtypes: EP1, EP2, EP3 and EP4. PGE2 participated in colon carcinogenesis via the EP1. PGE2 also participates in ovulation and fertilization and contributes to the control of blood pressure under high-salt intake via the EP2. PGE2 worked as a mediator of febrile responses to both endogenous and exogenous pyrogens and as a regulator of bicarbonate secretion induced by acid-stimulation in the duodenum via the EP3. It regulated the closure of ductus arteriosus and showed bone resorbing action via the EP4. PGD2 was found to be a mediator of allergic asthma. These studies have revealed important roles of prostanoids, some of which had not previously been known.

Topics: Animals; Asthma; Bicarbonates; Colonic Neoplasms; Dinoprost; Dinoprostone; Female; Fever; Hypertension; Inflammation; Labor, Obstetric; Mice; Mice, Knockout; Pregnancy; Prostaglandins; Receptors, Prostaglandin; Reproduction; Thrombosis; Thromboxane A2

The comparative safety of methods used to perform second-trimester abortion is an important public health concern. Morbidity and mortality studies have indicated that dilation and evacuation (D&E) is safer than instillation abortion, which is safer than hysterotomy and hysterectomy. In the third phase of the Joint Program for the Study of Abortion, the adjusted relative risk of serious complications associated with the intraamniotic instillation of urea and prostaglandin F2 alpha (the safest abortifacient regimen) was 1.9 times that associated with D&E (95% confidence interval, 1.2-3.1). An analysis of abortion mortality in the United States from 1972 to 1981 revealed a death-to-case rate of 4.9 per 100,000 abortions associated with D&E, 9.6 with instillation methods and over 60 with hysterotomy and hysterectomy. Little information exists concerning potential late sequelae of second-trimester abortion. D&E appears to be the safest method of second-trimester abortion available in the United States.. The comparative safety of methods used to perform 2nd-trimester abortion is an important public health concern. Morbidity and mortality studies have indicated that dilation and evacuation (D&E) is safer than instillation abortion, which is safer than hysterotomy and hysterectomy. In the 3rd phase of the Joint Program for the Study of Abortion, the adjusted relative risk of serious complications associated with the intraamniotic instillation of urea and prostaglandin F2alpha (the safest abortifacient regimen) was 1.9 times that associated with D&E (95% confidence interval, 1.2-3.1). An analysis of abortion mortality in the US from 1972-81 revealed a death-to-case rate of 4.9/100,000 abortions associated with D&E, 9.6 with instillation methods and over 60 with hysterotomy and hysterectomy. Little information exists concerning potential late sequelae of 2nd-trimester abortion. D&E appears to be the safest method of 2nd-trimester abortion available in the US.

Topics: Abortion, Induced; Abortion, Legal; Amnion; Blood Coagulation Disorders; Dilatation; Dilatation and Curettage; Dinoprost; Embolism, Amniotic Fluid; Female; Fever; Humans; Hysterectomy; Postoperative Complications; Pregnancy; Pregnancy Trimester, Second; Prostaglandins F; Risk; Saline Solution, Hypertonic; United States; Urea; Uterine Hemorrhage

Topics: Apudoma; Diarrhea; Dinoprost; Fever; Fingers; Foot Diseases; Humans; Hypercalcemia; Hypotension; Paraneoplastic Syndromes; Polycythemia; Prostaglandins; Prostaglandins E; Prostaglandins F

Oxidative stress (OS) contributes to the acute phase of Kawasaki disease (KD) in a manner that is as yet unknown. In the present study OS in the acute phase of KD was investigated by measuring urinary 8-iso-prostaglandin F2alpha (8-iso-PG) and evaluating its correlation to the efficacy of intravenous immunoglobulin (IVIG) administration.. The 62 patients with acute phase of KD were enrolled, as well as 20 healthy children (HC) and 20 with acute febrile illness (FI). Urinary samples were obtained before and after administration of IVIG. The HC and FI groups also had inflammatory markers evaluated at the same time. The 8-iso-PG was significantly elevated in the 62 KD patients (719 +/-335 pg/mg Cr) without IVIG administration compared with those with FI (583 +/-213 pg/mg Cr) as well as HC (443 +/-288 pg/mg Cr) (P<0.01). 40 patients were given 3 different regimens of IVIG: 16 received 2 g/kg for 1 day; 17 received 1 g/kg for 1 day; 7 received 400 mg . kg(-1) . day(-1) for 5 days. All regimens of IVIG reduced the 8-iso-PG level at 7 days after initiation.. OS provokes vasculitis in KD, the activation of which was reduced by IVIG. The urinary level of 8-iso-PG is a useful marker of the effectiveness of IVIG in the acute phase of KD.

Topics: Acute Disease; Acute-Phase Reaction; Biomarkers; Child; Child, Preschool; Dinoprost; Female; Fever; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Infant; Male; Mucocutaneous Lymph Node Syndrome; Oxidative Stress; Treatment Outcome

Twenty-four Quarter Horse and Quarter Horse-cross yearlings were experimentally infected with influenza A virus (Influenza A/equine/Saskatoon/90 [H3N8]) by nebulisation. In a double blind controlled trial the horses were randomly assigned to 3 groups of 8 animals. Group 1 received a placebo, (carrier syrup), Group 2 the labelled dose and Group 3 twice the labelled dose of clenbuterol hydrochloride. All treatments were given per os b.i.d. for 10 days and started on the day of infection. The horses were monitored for clinical signs of influenza infection for 14 days. Bronchoalveolar lavages were performed 4 days prior to, and 5 and 13 days after infection. Cell counts and concentrations of prostaglandin E2 and prostaglandin F2alpha in the lavage fluid were determined. Blood samples for haematology and serology were taken 4 days before, on the day of infection, 5, 9 and 13 days after infection. All horses experienced a typical influenza infection with fever, coughing and secondary bacterial infections with mainly Actinobacillus spp. and Streptococcus spp. There was no statistically or clinically significant effect of treatment with clenbuterol hydrochloride on measured clinical or laboratory parameters within 14 days of infection.

Topics: Adrenergic beta-Agonists; Animals; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Clenbuterol; Cough; Dinoprost; Dinoprostone; Double-Blind Method; Female; Fever; Horse Diseases; Horses; Influenza A virus; Leukocyte Count; Male; Orthomyxoviridae Infections

Matrix metalloproteinase (MMP)-2 deficiency makes humans and mice susceptible to inflammation. Here, we reveal an MMP-2-mediated mechanism that modulates the inflammatory response via secretory phospholipase A2 (sPLA2), a phospholipid hydrolase that releases fatty acids, including precursors of eicosanoids.. Mmp2(-/-) (and, to a lesser extent, Mmp7(-/-) and Mmp9(-/-)) mice had between 10- and 1000-fold elevated sPLA2 activity in plasma and heart, increased eicosanoids and inflammatory markers (both in the liver and heart), and exacerbated lipopolysaccharide-induced fever, all of which were blunted by adenovirus-mediated MMP-2 overexpression and varespladib (pharmacological sPLA2 inhibitor). Moreover, Mmp2 deficiency caused sPLA2-mediated dysregulation of cardiac lipid metabolic gene expression. Compared with liver, kidney, and skeletal muscle, the heart was the single major source of the Ca(2+)-dependent, ≈20-kDa, varespladib-inhibitable sPLA2 that circulates when MMP-2 is deficient. PLA2G5, which is a major cardiac sPLA2 isoform, was proinflammatory when Mmp2 was deficient. Treatment of wild-type (Mmp2(+/+)) mice with doxycycline (to inhibit MMP-2) recapitulated the Mmp2(-/-) phenotype of increased cardiac sPLA2 activity, prostaglandin E2 levels, and inflammatory gene expression. Treatment with either indomethacin (to inhibit cyclooxygenase-dependent eicosanoid production) or varespladib (which inhibited eicosanoid production) triggered acute hypertension in Mmp2(-/-) mice, revealing their reliance on eicosanoids for blood pressure homeostasis.. A heart-centric MMP-2/sPLA2 axis may modulate blood pressure homeostasis, inflammatory and metabolic gene expression, and the severity of fever. This discovery helps researchers to understand the cardiovascular and systemic effects of MMP-2 inhibitors and suggests a disease mechanism for human MMP-2 gene deficiency.

Topics: Animals; Cell Line; Dinoprost; Dinoprostone; Fever; Gene Expression Regulation; Inflammation; Matrix Metalloproteinase 2; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Phospholipases A2, Secretory; Polymerase Chain Reaction

Blockade of central endothelin ET(B) receptors inhibits fever induced by LPS in conscious rats. The contribution of ET(B) receptor-mediated mechanisms to fever triggered by intracerebroventricular IL-6, PGE2, PGF(2alpha), corticotropin-releasing factor (CRF), and preformed pyrogenic factor derived from LPS-stimulated macrophages (PFPF) was examined. The influence of natural IL-1 receptor antagonist or soluble TNF receptor I on endothelin (ET)-1-induced fever was also assessed. The selective ET(B) receptor antagonist BQ-788 (3 pmol icv) abolished fever induced by intracerebroventricular ET-1 (1 pmol) or PFPF (200 ng) and reduced that caused by ICV CRF (1 nmol) but not by IL-6 (14.6 pmol), PGE2 (1.4 nmol), or PGF(2alpha) (2 nmol). CRF-induced fever was also attenuated by bosentan (dual ET(A)/ET(B) receptor antagonist; 10 mg/kg iv) but unaffected by BQ-123 (selective ET(A) receptor antagonist; 3 pmol icv). alpha-Helical CRF(9-41) (dual CRF1/CRF2 receptor antagonist; 6.5 nmol icv) attenuated fever induced by CRF but not by ET-1. Human IL-1 receptor antagonist (9.1 pmol) markedly reduced fever to IL-1beta (180 fmol) or ET-1 and attenuated that caused by PFPF or CRF. Murine soluble TNF receptor I (23.8 pmol) reduced fever to TNF-alpha (14.7 pmol) but not to ET-1. The results of the present study suggest that PFPF and CRF recruit the brain ET system to cause ET(B) receptor-mediated IL-1-dependent fever.

Topics: Animals; Body Temperature; Corticotropin-Releasing Hormone; Dinoprost; Dinoprostone; Endothelin B Receptor Antagonists; Etanercept; Fever; Immunoglobulin G; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Lipopolysaccharides; Male; Peptide Fragments; Pyrogens; Rats; Rats, Wistar; Receptor, Endothelin B; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Sialoglycoproteins

The objective of this study was to evaluate the efficacy of a blanket systemic preventive treatment (PT) of cows having retained fetal membranes (RFM) with 1 mg/kg of ceftiofur administered the first day after calving regardless of their body temperature. This strategy was compared with a selective treatment (ST) strategy in which only cows having RFM and a rectal temperature > or = 39.5 degrees C within 10 d postpartum received ceftiofur. Cows that retained their fetal membranes for at least 24 h after calving were allocated to 2 groups. Rectal temperature was measured daily for 10 d postpartum. Sixty PT cows having RFM received a daily ceftiofur (1 mg/kg of body weight) treatment, administered subcutaneously during the first 3 d after diagnosis of RFM. If rectal temperature was > or = 39.5 degrees C after 3 daily treatments, cows received ceftiofur for 2 more days. Therapy in 53 ST cows was based on selective administration of ceftiofur to cows having fever during the first 10 d postpartum. Treatment was conducted for 3 to 5 consecutive days as described for PT cows, beginning on the first day of fever. In both groups, manual removal of the placenta was not attempted and antibiotic drugs were not administered into the uterus. For every cow having RFM enrolled in PT or ST, 1 cow without RFM that had calved on the same day was enrolled in a healthy control group (n = 113). All cows received two 25-mg doses of PGF(2alpha): 1 dose between 18 and 24 d and 1 dose between 32 and 38 d postpartum. The PT did not reduce the proportion of cows experiencing fever during 10 d postpartum compared with ST cows (71.7 vs. 69.8%). Results were compared using logistic regression models and survival analyses. The artificial insemination submission rate between 42 and 62 d postpartum was greater in PT (41.2 vs. 20.8 vs. 24.5%), but total conception rate was less in ST and control cows, respectively (25.0 vs. 38.9 vs. 36.2%). In this trial, a preventive systemic antibiotic treatment of all cows having RFM was not superior to a selective antibiotic treatment of cows only in case of fever.

Topics: Animals; Anti-Bacterial Agents; Body Temperature; Cattle; Cattle Diseases; Cephalosporins; Dinoprost; Female; Fever; Insemination, Artificial; Logistic Models; Placenta, Retained; Postpartum Period; Pregnancy; Reproduction

This study evaluates the antipyretic activity of nimesulide, a cyclooxygenase (COX-2) selective inhibitor in rats. The effects of nimesulide on lipopolysaccharide (LPS)-induced cerebrospinal prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) and on plasma tumor necrosis factor-alpha (TNF-alpha) levels were also evaluated. Male Wistar rats received an i.p. injection of LPS, or i.c.v. injections of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), TNF-alpha, macrophage inflammatory protein-1alpha (MIP-1alpha), arachidonic acid, PGE(2), PGF(2alpha), corticotrophin-releasing factor (CRF) or endothelin-1 (ET-1). Nimesulide or indomethacin administered i.p 30 min prior LPS, IL-1beta, IL-6, TNF-alpha or arachidonic acid reduced the febrile response and PGE(2) or PGF(2alpha) levels in LPS-febrile rats but did not modify PGE(2)-induced fever. Nimesulide, but not indomethacin, reduced the fever induced by MIP-1alpha, PGF(2alpha), CRF or ET-1. Plasma TNF-alpha levels in LPS-treated rats were also reduced by nimesulide. These findings confirm that the antipyretic effect of nimesulide differs from the antipyretic scenario with the non-selective cyclooxygenase blocker indomethacin. Additional mechanisms, including inhibition of increased plasma TNF-alpha, may contribute to its antipyretic activity in rats.

Topics: Analgesics, Non-Narcotic; Animals; Arachidonic Acid; Body Temperature; Chemokine CCL3; Chemokine CCL4; Corticotropin-Releasing Hormone; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Endothelin-1; Fever; Indomethacin; Injections, Intraperitoneal; Injections, Intraventricular; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Macrophage Inflammatory Proteins; Male; Rats; Rats, Wistar; Sulfonamides; Time Factors; Tumor Necrosis Factor-alpha

It was previously shown that sustained fever can be induced in rats by central injection of endothelin-1 (ET-1). This peptide appears to participate in the mechanism(s) of LPS-induced fever, which is reduced by pretreatments with ET(B) receptor antagonists. In this study, we compared the effects of a nonselective cyclooxygenase (COX) inhibitor, indomethacin, with those of two selective COX-2 inhibitors, celecoxib and lumiracoxib, on ET-1-induced fever in rats. Fever induced in conscious animals by ET-1 (1 pmol icv) or LPS (5 mug/kg iv) was prevented by pretreatments with celecoxib (5 and 10 mg/kg) or lumiracoxib (5 mg/kg) given by oral gavage 1 h before stimuli. Lower doses of celecoxib had partial (2.5 mg/kg) or no effect (1 mg/kg). Indomethacin (2 mg/kg ip) partially inhibited fever induced by LPS but had no effect on ET-1-induced fever. The levels of PGE(2) and PGF(2alpha) in the cerebrospinal fluid (CSF) of pentobarbital sodium-anesthetized rats were significantly increased 3 h after the injection of LPS or ET-1. The latter increase was abolished by celecoxib at all tested doses and by indomethacin. In conclusion, selective COX-2 inhibitors were able to prevent ET-1-induced fever, indicating a role for COX-2 in this phenomenon. However, the fact that reduced CSF PG levels obtained with indomethacin and a low dose of celecoxib are not accompanied by changes in fever induced by ET-1, along with the lack of inhibitory effects of indomethacin on ET-1 fever, suggests that the latter might also involve COX-2-independent mechanisms.

Topics: Animals; Celecoxib; Cyclooxygenase Inhibitors; Diclofenac; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Endothelin-1; Fever; Indomethacin; Injections, Intraperitoneal; Injections, Intraventricular; Intubation, Gastrointestinal; Lipopolysaccharides; Male; Organic Chemicals; Pyrazoles; Rats; Rats, Wistar; Sulfonamides

Bacterial cell walls contain peptidoglycan (PTG), which, among other actions, induces fever. The present experiment evaluated the effects of PTG treatment on early pregnancy and blood plasma concentrations of reproductive hormones. Ewes were injected i.v. with saline or 15, 30 or 60 microg kg(-1) sonicated PTG (Streptococcus pyogenes) on day 5 after mating. Each dose of PTG induced fever. Pregnancy rate at day 25 was not related to incidence of fever but tended to differ among treatments (control, 100%; low, 100%; medium, 67%; high, 60%; P < 0.08). Combined pregnancy rate in ewes from control and low dose groups (100%) was greater than that in ewes from medium and high dose groups (64%, P < 0.01). Ewes with high 13,14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM) concentrations had lower pregnancy rates (6 of 10) than those with low concentrations of PGFM (11 of 11; P < 0.05). Mean cortisol concentrations were higher in treated (2.8 +/- 0.28 microg dl(-1)) than in control (1.1 +/- 0.03 microg dl(-1)) ewes (P < 0.01); the pattern of secretion was biphasic and increased in all treated ewes (P < 0.01). Neither means nor profiles of oestradiol differed with treatment. Mean concentrations and the pattern of concentrations of progesterone were reduced in all treated ewes, as indicated by the time by treatment and linear interaction with treatment (1.2 +/- 0.1 versus 1.6 +/- 0.1 ng ml(-1), P < 0.01). Patterns of LH pulses did not differ from 0 to 4 h or 24 to 28 h after treatment; mean plasma LH concentration was lower in ewes treated with 0, 15 or 30 microg PTG kg(-1) than with 60 microg PTG kg(-1) (P < 0.01). Pregnancy status was not related to plasma concentrations or patterns of LH, oestradiol, progesterone or cortisol. Inflammatory mediators, such as PGF(2alpha), may act directly on the embryo or uterus in ewes treated with PTG.

Topics: Abortion, Septic; Animals; Dinoprost; Estradiol; Female; Fever; Hydrocortisone; Luteinizing Hormone; Peptidoglycan; Pregnancy; Progesterone; Sheep; Sheep Diseases; Streptococcal Infections; Streptococcus pyogenes

Experiments compared the hemispheric neural damage resulting from global hemispheric hypoxic ischemia (GHHI, ligation of right common carotid artery plus 35 min of 12% O2) in groups of anesthetized, male Long Evans rats, 9-10 weeks of age, kept at 37 degrees C, and previously given an intracerebroventricular (i.c.v., 2.5 microl) injection of 28 or 70 pmoles of PGE2, PGF2alpha or PGD2 or sterile saline (SS) 30 min beforehand. Mean arterial pressure (MAP), ipsilateral cortical capillary blood flow (CBF), colonic (Tc), ipsilateral (Tipsi) and contralateral (Tcontra), temporalis muscle temperatures were measured before, during and for 15 min after GHHI. Necrotic neural damage was assessed 7 days post-GHHI. All groups given GHHI + PGs showed increased ipsilateral hemispheric damage to GHHI especially due to enhanced neocortical damage, compared to the saline control group given the same insult. PGD2 was the most potent PG to cause further damage to the global insult. Tc, Tipsi, Tcontra and MAP increased following the i.c.v. injection of PGE2. I.c.v. PGF2alpha transiently decreased MAP, PGD2 tended to decrease cerebral blood flow and neither evoked changes in temperature compared to respective pre-injection control values. Results demonstrate increased neural damage to GHHI with prior i.c.v. PGE2, PGF2alpha or PGD2 administration.

Topics: Animals; Body Temperature; Brain; Brain Ischemia; Dinoprost; Dinoprostone; Fever; Hemodynamics; Hypoxia, Brain; Male; Prostaglandin D2; Rats

Topics: Animals; Dinoprost; Dinoprostone; Female; Fever; Lipopolysaccharides; Malondialdehyde; Methylene Blue; Nitric Oxide; Pyrogens; Rabbits; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

We investigated the effects of intraperitoneal administration of adrenoceptor antagonists to the hyperthermia and hyperglycemia induced by prostaglandin F2 alpha (50 micrograms) injected into the third cerebral ventricle in anesthetized rats. Phentolamine inhibited the hyperthermia and hyperglycemia induced by prostaglandin F2 alpha. Prazosin inhibited the hyperthermia induced by prostaglandin F2 alpha, while enhancing the hyperglycemia. Yohimbine inhibited the prostaglandin F2 alpha-induced hyperglycemia without an effect on the hyperthermia. Propranolol had no effect on either prostaglandin F2 alpha-induced hyperglycemia or hyperthermia. These observations suggest that the hyperglycemia induced by prostaglandin F2 alpha is regulated by alpha 2-adrenoceptor systems while the hyperthermia is regulated by alpha 1-adrenoceptor systems in rats.

Topics: Adrenergic alpha-Antagonists; Animals; Blood Glucose; Body Temperature; Dinoprost; Fever; Hyperglycemia; Injections, Intraperitoneal; Injections, Intraventricular; Male; Phentolamine; Prazosin; Propranolol; Rats; Rats, Wistar; Yohimbine

1. The actions of peripheral arginine vasopressin (AVP) on the febrile responses of conscious rabbits induced by peripherally administered polyinosinic:polycytidylic acid (poly(I).poly(C)) have been studied using an AVP V1 receptor antagonist ([deamino-Pen1, O-Me-Tyr2, Arg8]-vasopressin). 2. Temperature responses were monitored continuously using rectal thermistor probes. Test substances were administered intravenously (i.v.). Blood samples were taken at timed intervals from a marginal ear vein and plasma PGE2 and PGF2 alpha levels determined by radioimmunoassay. 3. Poly(I).poly(C) (2.5 micrograms/kg) stimulated a reproducible biphasic rise in body temperature with a lag phase of 45-60 min and peaks at 90 and 225 min. The febrile response was accompanied by a 5-fold rise in circulating immunoreactive (ir) PGE2, which peaked after 90 min and remained elevated up to 300 min. Poly(I).poly(C) also stimulated a 2.5-fold rise in circulating irPGF2 alpha, which peaked after 150 min and was followed by a return to basal levels after 300 min. 4. The overall magnitude of the febrile response to poly(I).poly(C) (2.5 micrograms/kg, i.v.) was significantly antagonized by the AVP V1 receptor antagonist (250 micrograms/kg, i.v.) administered 5 min prior to the pyrogen. 5. The irPGE2 response to poly(I).poly(C) (2.5 micrograms/kg, i.v.) was significantly antagonized by the AVP V1 receptor antagonist (250 micrograms/kg, i.v.) administered 5 min prior to the pyrogen. The irPGF2 alpha response was only reduced at the peak 150 min time point measurement. 6. In conclusion, these results show a modulatory role for a peripherally administered AVP V1 antagonist in the febrile responses to poly(I).poly(C), suggesting a possible propyretic role for endogenous peripheral AVP. This modulatory role appears to be mediated via actions on prostaglandin E2.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Body Temperature; Dinoprost; Dinoprostone; Fever; Interferon Inducers; Male; Poly I-C; Rabbits; Vasopressins

The effect of dexamethasone on prostaglandin (PG) E2- and PGF2 alpha-induced fever was studied in rats. Intracerebroventricular injection of PGE2 and PGF2 alpha (500 ng) induced increases in body temperature (maximal temperature rises of 0.97 +/- 0.13 degrees C and 0.78 +/- 0.18 degrees C, respectively, vs. vehicle 0.12 +/- 0.09 degrees C) of unrestrained rats maintained within the thermoneutral zone. PGE2-induced fever peaked earlier and the defervescence was faster when compared to the response induced by PGF2 alpha. Subcutaneous pre-administration of dexamethasone (0.5 mg/kg) did not affect PGE2-induced fever (maximal temperature rise of 1.00 +/- 0.08 degrees C), but completely prevented the pyrogenic activity of PGF2 alpha (maximal temperature rise of 0.16 +/- 0.16 degrees C). Neither PGE2- nor PGF2 alpha-induced fever was significantly altered (maximal temperature rises of 0.90 +/- 0.11 degrees C and 0.64 +/- 0.14 degrees C, respectively) by intraperitoneal administration of indomethacin (2 mg/kg). These results demonstrate for the first time that glucocorticoids, in addition to inhibiting endotoxin- and cytokine-induced fever, can also modulate the pyrogenic activity of some prostaglandins, possibly via suppression of the synthesis of corticotropin-releasing factor, indicating that multiple mechanisms may be involved in the antipyretic activity of these steroids.

Topics: Animals; Body Temperature; Dexamethasone; Dinoprost; Dinoprostone; Fever; Indomethacin; Injections, Subcutaneous; Male; Pyrogens; Rats; Rats, Sprague-Dawley

We previously reported that intraventricular prostaglandins (PGs) produced hyperthermia and hyperglycemia in anesthetized rats. However, the relationship of them is little known. We examined the relationship between hyperthermia and hyperglycemia induced by intraventricular PGF2 alpha using curarized and adrenal demedullated rats. Iv curare completely prevented the PGF2 alpha-induced hyperthermia, but enhanced the hyperglycemic effect of PGF2 alpha. Adrenal demedullation completely prevented the hyperglycemia, but did not affect the hyperthermic effect of PGF2 alpha. To further assess the site of action concerned with PGF2 alpha-induced thermoregulation and glucoregulation in the central nervous system (CNS), we injected saline or PGF2 alpha into the preoptic area of the anterior hypothalamus (POA) in intact rats. After microinjection of PGF2 alpha into the POA, the rectal temperature rose, but the plasma glucose level did not increase significantly, as compared with saline-treated control rats. These results suggest that PGF2 alpha causes the central nervous system to produce hyperthermia via shivering, stimulated the somatic motor system, and to produce hyperglycemia by stimulating central sympathetic outflow to the adrenal medulla, but these operate independently under different neural regulation, and these sensitive sites are organically dissociated in the CNS.

Topics: Adrenal Medulla; Adrenalectomy; Animals; Blood Glucose; Body Temperature; Cerebral Ventricles; Curare; Dinoprost; Fever; Hyperglycemia; Injections, Intravenous; Injections, Intraventricular; Kinetics; Male; Rats; Rats, Inbred Strains

The effects of hypothermia and hyperthermia on the cerebral microcirculation were studied using isolated perfused intracerebral (parenchymal) arterioles obtained from rats. In a temperature-dependent manner, hypothermia (20.0 degrees to 35.0 degrees C) dilated the spontaneous tone developed by the arterioles and also diminished their contractile response to potassium and prostaglandin F2 alpha. In contrast, hyperthermia (40.0 degrees to 45.0 degrees C) induced a biphasic response consisting of initial vasoconstriction and secondary vasodilation. Exposure of the vessels to 45.0 degrees C for 30 minutes irreversibly abolished the spontaneous tone and responsiveness of the arterioles when the temperature of the preparation was returned to 37.5 degrees C. In calcium-free solutions, however, the arteriolar diameter was not affected within a temperature range of 20.0 degrees to 45 degrees C. Furthermore, arterioles that had been in a calcium-free solution during exposure to 45 degrees C temperature recovered their viability at 37.5 degrees C. These results suggest that changes in ambient temperature alter calcium-induced contraction in arteriolar smooth muscle, and that the irreversible effects of hyperthermia on the arterioles are dependent upon extracellular calcium. These studies indicate that alterations in brain temperature may affect the pathogenesis of cerebral ischemia by mechanisms that are in part independent of parenchymal metabolism.

Topics: Analysis of Variance; Animals; Arterioles; Calcium; Cerebrovascular Circulation; Dinoprost; Fever; Hydrogen-Ion Concentration; Hypothermia; In Vitro Techniques; Potassium; Rats; Vasoconstriction; Vasodilation

Infusion of the prostaglandin synthetase inhibitor 4-aminoantipyrine at a rate of 20 mg/min via the fetal tarsal vein during normothermic conditions (ambient temperatures = 24 degrees C) significantly decreased the concentrations of prostaglandins E2 and F2 alpha in maternal and fetal arterial plasma and in uterine and umbilical vein plasma. The infusion was associated with a small but significant rise in fetal temperature and a fall in fetal arterial pH. Respiratory alkalosis developed in fetuses during hyperthermia by raising the ambient temperature to 43 degrees C for 8 hours. In contrast, infusion of 4-aminoantipyrine during hyperthermia produced fetal metabolic acidosis as indicated by a fall in fetal pH and an increase in PaCO2, even though the ewe remained hypocapnic. Four of the 10 fetuses died during or shortly after the 4-aminoantipyrine infusion during hyperthermia. These results indicate that uteroplacental prostaglandin synthesis is essential to allow the fetus to adapt to an increase in body temperature and suggests that prostaglandin synthetase inhibitors should be used with caution during pregnancy.

Topics: Ampyrone; Animals; Antipyrine; Blood Gas Analysis; Blood Glucose; Body Temperature; Dinoprost; Dinoprostone; Female; Fetal Blood; Fever; Pregnancy; Pregnancy, Animal; Prostaglandin Antagonists; Prostaglandins; Reference Values; Regional Blood Flow; Sheep; Uterus

To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.

Topics: Animals; Body Temperature; Dinoprost; Dinoprostone; Endotoxins; Fever; Humans; Interleukin-1; Lipopolysaccharides; Male; Prostaglandins E; Prostaglandins F; Pyrogens; Rabbits; Recombinant Proteins; Skin Temperature

1. The effects of microinjection of prostaglandin D2, E2 and F2 alpha and of endogenous pyrogen on the rectal temperature of rabbits were extensively examined in sixty-eight brain regions and in the third cerebral ventricle. 2. Intracerebroventricular injection of both prostaglandins E2 and F2 alpha produced dose-dependent fever over a range of 100-1000 ng. The selective brain regions, the nucleus broca ventralis, preoptic area, anterior hypothalamus and the ventromedial hypothalamus, responded to microinjections of a small dose (less than 200 ng) of prostaglandins E2 and F2 alpha by producing fever. Furthermore, the lateral hypothalamus, ventral thalamus, substantia nigra and the trigeminal nucleus were also sensitive to high concentrations of prostaglandins E2 and F2 alpha, fever being produced. It is likely that prostaglandin D2 is not involved in fever induction. 3. The ventricular injection of endogenous pyrogen also produced fever. However, brain regions sensitive to microinjection of endogenous pyrogen were exclusively localized to regions near the organum vasculosum laminae terminalis (OVLT), such as the nucleus broca ventralis and the preoptic area. In contrast to the monophasic fever induced by prostaglandins E2 and F2 alpha, about 30 min after ventricular or cerebral injection of endogenous pyrogen the rectal temperature gradually started to rise and the fever was prolonged over 4 h. 4. We investigated the effect of an inhibitor of prostaglandin synthesis, sodium salicylate, on biphasic fever induced by intravenous injection of bacterial endotoxin. The microinjections of sodium salicylate into the bilateral regions near the OVLT suppressed the second peak but had no effect on the first peak. 5. The present study clarifies that there exist two separate mechanisms of induction of biphasic fever. Correlating with the first peak of biphasic fever, prostaglandins synthesized outside the blood-brain barrier act on multiple sites in the central nervous system to induce fever. Correlating with the second peak, endogenous pyrogen acts on regions near the OVLT to synthesize and release pyrogenic prostaglandins.

Topics: Animals; Body Temperature; Brain; Cerebral Ventricles; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Fever; Injections, Intraventricular; Interleukin-1; Male; Prostaglandin D2; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; Rabbits; Time Factors

Intravenous infusion of Pasteurella hemolytica endotoxin caused marked increases in the plasma levels of thromboxane B2 (TxB2), prostaglandins (PG) and serotonin in sheep. The control values for TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and serotonin before endotoxin infusion averaged 283 +/- 53 (standard error of mean), 281 +/- 14 and 199 +/- 27 pg/ml and 57 +/- 3 ng/ml, respectively. At 50 min during endotoxin infusion, these values were increased to their maximum of 376, 339, 325 and 202% of control, respectively. Body temperature increased from the control value of 39.5 +/- 0.1 degrees C to a maximum of 41.5 +/- 0.1 degrees C at 200-300 min of infusion. In the second part of this study, we have examined the effects of ibuprofen on endotoxin-induced increases in plasma PG, TxB2, and serotonin levels and body temperature. The control values for TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and temperature prior to ibuprofen and endotoxin infusion averaged 238 +/- 35, 335 +/- 44 and 248 +/- 28 pg/ml, 65 +/- 3 ng/ml and 40.1 +/- 0.2 degrees C, respectively. A loading dose (15 mg/kg) of ibuprofen was followed by infusion of endotoxin (12 micrograms/kg) and ibuprofen (43.3 mg/kg) over 500 min. Plasma levels of 6-keto-PGF1 alpha and serotonin increased only to 131 and 149% of control at 50 min of infusion, and levels of PGF2 alpha and TxB2 decreased to 50 and 80% of control at 100 and 150 min of infusion, respectively. Temperature remained unchanged. Ibuprofen effectively suppressed endotoxin-induced increases in the plasma levels of TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and serotonin and body temperature. It was concluded from the present study that nonsteroidal anti-inflammatory drugs as an adjunct to antibiotic therapy might have a rational basis in treatment of endotoxin toxicity.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprost; Endotoxins; Female; Fever; Ibuprofen; Pasteurella; Pasteurella Infections; Prostaglandins; Prostaglandins F; Serotonin; Sheep; Sheep Diseases; Thromboxane B2; Thromboxanes

Responses to intravenous injections of an endotoxin (E. coli-lipopolysaccharide, 1 microgram/kg b.wt.) and endogenous pyrogen were studied in euhydrated and hyperhydrated goats. The biphasic febrile response to the endotoxin was associated with a pronounced increase in the renal excretion of measured prostaglandin (PG) metabolites (11-ketotetranor PGF metabolites). This increase was time-correlated with the elevation of the rectal temperature, and (in hyperhydrated animals) with an inhibition of the water diuresis and an increase in renal excretion of arginine vasopressin (AVP). Other effects of the endotoxin were an immediate depression of renal Na and K excretion followed by the development of pronounced natriuresis, and a reduction of plasma Fe and Zn concentrations. The appearance of the febrile reactions (peripheral vasoconstriction and shivering) was accompanied by miosis. The maximum elevation of the rectal temperature was significantly greater during euhydration than during hyperhydration. Also endogenous pyrogen elicited miosis concomitant with febrile reactions, and an elevation of the renal excretion of PG metabolites which was closely correlated in time with the monophasic febrile response, and (during hyperhydration) with temporary inhibition of the water diuresis and an increase in the renal AVP excretion. However, the responses were much weaker than the corresponding endotoxin effects. No appreciable changes in renal excretion of Na and K were observed in response to the endogenous pyrogen. It is concluded that the observed effects on renal cation excretion were manifestations of direct endotoxin influences on kidney function.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arginine Vasopressin; Body Temperature; Dinoprost; Endotoxins; Escherichia coli; Female; Fever; Goats; Kidney; Lipopolysaccharides; Natriuresis; Potassium; Prostaglandins F; Pupil; Pyrogens; Sodium

Although dilatation and evacuation (D&E) is currently the most common method of midtrimester abortion in the United States, the intra-amniotic instillation of hyperosmolar urea and prostaglandin F2 alpha combined (U-P) has been proposed as a safer technique. To evaluate the comparative safety of U-P and D&E, we analyzed 2,805 U-P and 9,572 D&E abortions at 13 to 24 menstrual weeks' gestation. The U-P procedure resulted in significantly more serious complications than D&E (1.03 v 0.49 per 100 abortions). After adjusting for patient age, race, parity, follow-up information, and preexisting conditions, the relative risk of serious complications associated with U-P was 1.9 (95% confidence interval, 1.2 to 3.1). This advantage for D&E stems from its applicability to the 13- to 16-week interval. Although D&E appears to be safer overall in the midtrimester, for women obtaining abortion after 16 weeks, the rates of serious complications were comparable, with a relative risk of 1.0 (95% confidence interval, 0.4 to 2.5).

Topics: Abortion, Induced; Amnion; Cervix Uteri; Dilatation and Curettage; Dinoprost; Endometritis; Female; Fever; Gestational Age; Humans; Hypertonic Solutions; Laminaria; Pregnancy; Pregnancy Trimester, Second; Prostaglandins F; Urea; Uterine Hemorrhage