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D Soszynski

Publications and source records attributed to D Soszynski.

At least 19 recordsLinked to original sources
PubMed2001

The inhibition of nitric oxide synthase suppresses LPS- and psychological-stress-induced fever in rats.

The purpose of this study was to assess the effects of a non-selective nitric oxide synthase (NOS) inhibitor on changes in fever response due to injection of lipopolysaccharide (LPS) or on stress fever caused by exposure to an open field in freely moving biotelemetered rats. N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of all NOS-isoforms, was injected intraperitoneally (ip) at a dose of 50 mg/kg just before intraperitoneal injection of LPS at a dose of 50 microg/kg or exposure to open field. L-NAME at a dose of 50 mg/kg had no effect on normal day-time body temperature (T(b)) and normal night-time T(b). The same dose of L-NAME administered intraperitoneally caused a significant attenuation of LPS-induced fever. The thermal index calculated for rats pretreated with L-NAME and injected with LPS was reduced by approximately 75% compared to that calculated for saline-pretreated and LPS-injected rats. To examine the effect of NOS inhibition on psychological-stress-induced elevation in T(b), rats were injected intraperitoneally with L-NAME and then immediately exposed to open field for 60 min. After exposure to the open field, rats not treated with NOS inhibitor responded with a rapid rise in T(b), and it was accompanied with an increase of motor activity. L-NAME significantly suppressed the stress fever without any effect on changes in motor activity. Presented data provide clear evidence that NO formation is involved in LPS- and psychological-stress-induced fevers in rats.

Animals↗
PubMed2000

Blockade of nitric oxide formation enhances thermal and behavioral responses in rats during turpentine abscess.

OBJECTIVE: The purpose of this study was to investigate the role of nitric oxide (NO) during the development of fever and other symptoms of sickness behavior (i.e. anorexia, cachexia) in response to localized tissue inflammation caused by injection of turpentine in freely moving biotelemetered rats. METHODS: To determine the role of NO in turpentine-induced fever, we injected the NO synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) intraperitoneally simultaneously or 5 h after turpentine injection. RESULTS: Rats responded with fever to intramuscular injection of 20 microl of turpentine that commenced 6 h after injection and reached peak values 11 h after injection. Although turpentine did not significantly alter food and water intake, it caused a drop in body weight. Rats injected with turpentine and treated with L-NAME responded with a substantial rise in fever, independently of the time of L-NAME injection. The rise in body temperature (T(b)) due to turpentine injection began slightly sooner and reached the maximal T(b) value faster in rats treated with L-NAME than in the ones treated with saline (control for L-NAME). The enhanced decrease in food and water intake in rats treated with a combination of L-NAME and turpentine was also observed. As a result, L-NAME-injected rats responded with a profound drop in body mass due to turpentine, independently of the time of L-NAME injection. L-NAME alone did not affect food and water intake, but slightly suppressed the gain of body mass. CONCLUSION: These results indirectly indicate that NO is involved in pyrogenic and behavioral responses in rats during turpentine abscess.

Animals↗
PubMed1998

Endotoxin tolerance does not alter open field-induced fever in rats.

Exposure to an open field has been shown to cause a rise in the body temperature of rats. In many respects, this rise in body temperature is similar to fevers caused by endotoxin and other inflammatory stimuli. Rats repeatedly injected with endotoxin develop tolerance to the fever-inducing action of endotoxin. We hypothesized that repeated pretreatment with endotoxin would modify the fever caused by exposure to psychological stress. To test this hypothesis, we compared open field-induced fevers in rats made endotoxin tolerant to those rats not endotoxin tolerant. We found that endotoxin tolerance had no effect on open field fevers.

Animals↗
PubMed1998

Effect of nicotine on the immune system: possible regulation of immune responses by central and peripheral mechanisms.

Nicotine (NT) treatment impairs T-cell receptor (TCR)-mediated signaling, leading to the arrest of T cells in the G1 phase of the cell cycle and inhibition of the antibody plaque-forming cell (AFC) response to sheep red blood cells (SRBC). This paper summarizes some of the previous findings related to cigarette smoke/NT and the immune response, and presents preliminary evidence suggesting that mice chronically treated with NT (0.5 mg/day/kg body weight) have a depressed inflammatory response in the turpentine-induced abscess model of inflammation. This ability of nicotine to attenuate an inflammatory response may also be the cause of reduced mortality of chronically nicotine-treated mice from acute influenza A pneumonitis. Moreover, in LEW rats, decreased anti-SRBC AFC responses were also observed after intracerebroventricular (i.c.v.) administration of relatively small concentrations of NT (28 micrograms/day/kg body weight) which, when given peripherally, did not affect the AFC response. In vitro the addition of NT to T cells increased protein tyrosine kinase (PTK) activity and intracellular Ca2+ concentration [Ca2+]i. These results support the hypothesis that NT alters immune responses by directly interacting with T cells, as well as indirectly through brain-immune interactions.

Abscess↗
PubMed1997

Sickness behavior in mice deficient in interleukin-6 during turpentine abscess and influenza pneumonitis.

Interleukin-6 (IL-6), among other cytokines, is thought to be involved in the regulation of sickness behavior (e.g., anorexia, cachexia, fever, and lethargy) induced by infections bacterial and viral origin) and sterile tissue necrosis (burns and surgical traumas). Mice deficient in IL-6 (IL-6 KO) were generated by gene targeting. Homozygous IL-6 KO male and female mice and their appropriate controls were implanted with biotelemeters to monitor body temperature (Tb) and motor activity (Act). Normal circadian rhythms in Tb and Act as well as rates of food intake and weight gain did not differ significantly between sex-matched IL-6 KO and control groups at 30 degrees C in a 12:12-h light-dark cycle. Sterile tissue damage was induced in mice by subcutaneous injection of turpentine (0.1 ml, left hindlimb). Influenza pneumonitis was induced by intranasal inoculation of mouse-adapted influenza A virus (17.5 plaque-forming units). Lack of IL-6 completely prevented fever, anorexia, and cachexia because of turpentine abscess in both sexes. It did not prevent lethargy, although IL-6 KO mice recovered to normal Act significantly sooner than wild-type mice. Symptoms of sickness were only slightly modified during influenza virus infection in IL-6 KO mice. Attenuation of sickness behavior was more pronounced in IL-6 KO female than in male mice. We conclude that, although IL-6 is induced during both turpentine abscess and influenza infection, this cytokine appears to be more critical in induction of the symptoms of sickness behavior during sterile tissue abscess than during influenza infection.

Abscess↗
PubMed1997

Dietary n-3 fatty acids differentially affect sickness behavior in mice during local and systemic inflammation.

We tested the hypothesis that increased dietary fish oil levels (via modulation of the production of inflammatory mediators) modulate sickness symptoms (i.e., anorexia, cachexia, fever, lethargy) of systemic and local inflammation. Swiss Webster mice were implanted with biotelemeters to measure body temperature and motor activity and were fed a diet high in n-3 fatty acids (17% wt/wt menhaden oil) or a reference diet (17% wt/wt hydrogenated coconut oil or normal rodent chow) for 6 wk. Local inflammation was induced by subcutaneous injection of turpentine (100 microl/mouse). Systemic inflammation was elicited by intraperitoneal injection of lipopolysaccharide (LPS; 2.5 mg/kg). Fever, lethargy, anorexia, and weight decrease during turpentine abscess were all inhibited (P < 0.05) in mice fed the fish oil diet. Indomethacin, similar to the fish oil diet, attenuated the turpentine-induced symptoms in mice fed a normal diet. Dietary n-3 fatty acids prevented fever and attenuated the decrease in body weight caused by LPS but did not affect the LPS-induced lethargy and anorexia. Within 90 min of LPS injection, the bioactivity of plasma tumor necrosis factor-alpha (TNF-alpha) increased to 98.2 +/- 5.1 ng/ml in mice fed fish oil compared with 32.6 +/- 3.6 ng/ml in those fed the reference diet (P < 0.05). Plasma prostaglandin E2 (PGE2) levels after LPS injection of mice fed the control diet increased within 90 min to 16.4 +/- 5.1 pg/ml. Mice fed the fish oil diet did not show any elevation in plasma PGE2 levels at that time (P < 0.05). We speculate that dietary n-3 fatty acids suppressed PGE2-related responses, including a PGE2-dependent negative feedback on TNF-alpha production, which resulted in differential modulation of sickness behavior depending on the locus of inflammation.

Animals↗
PubMed1997

Effect of heat stress on LPS-induced fever and tumor necrosis factor.

Exposure to heat stress leads to both short-term and long-term effects on morbidity. Male rats were exposed to a high ambient temperature of 40 degrees C, which resulted in biotelemetered core body temperature rising to approximately 42 degrees C. This treatment led to a marked enhancement in lipopolysaccharide (LPS)-induced fever at 24 h after exposure to heat stress. The increase in fever was accompanied by a significant suppression in the circulating concentration of tumor necrosis factor. Heat-shock protein-70 measured in liver was elevated by the heat exposure (but not further elevated by the injection of LPS). An enhanced fever to LPS and other inflammatory stimuli found in heat-stressed human subjects could explain the apparent increase in susceptibility to disease.

Animals↗
PubMed1996

The adaptive value of fever.

There is overwhelming evidence in favor of fever being an adaptive host response to infection that has persisted throughout the animal kingdom for hundreds of millions of years. As such, it is probable that the use of antipyretic/anti-inflammatory/analgesic drugs, when they lead to suppression of fever, results in increased morbidity and mortality during most infections; this morbidity and mortality may not be apparent to most health care workers because fever is only one of dozens of host defense responses. Furthermore, most infections are not life-threatening and subtle changes in morbidity are not easily detected.

Adaptation, Physiological↗
PubMed1996

Beta-adrenoceptor antagonists suppress elevation in body temperature and increase in plasma IL-6 in rats exposed to open field.

The purpose of these studies was to assess the involvement of beta-adrenoceptors in the development of psychological stress-induced elevation in body temperature (Tb) and rise in circulating interleukin-6 (IL-6). We selected three drugs to attempt to block the rise in body temperature and plasma IL-6; L-propranolol, D-propranolol and nadolol. Both stereoisomers of propranolol have "local anesthetic' membrane-stabilizing activity and are capable of penetrating into the brain. However, D-propranolol has significantly lower beta-blocking activity than L-propranolol. Nadolol has beta-blocking activity similar to L-propranolol without membrane-stabilizing activity. Furthermore, nadolol does not cross the blood-brain barrier. All beta-blockers were injected intraperitoneally (i.p. 7.5 mg/kg) or into the third cerebral ventricle (i.c.v., 5 or 50 micrograms/animal), 20 min or just before exposure of rats to an open field, respectively. Blood samples for measurement of plasma IL-6 activity (IL-6-dependent B9 cell bioassay) were taken from rats immediately following exposure to the open field. After exposure to the open field, rats not treated with beta-blockers responded with a rapid rise in Tb measured by biotelemetry as well as with an increase in plasma IL-6 activity. The increase in Tb of open field-exposed rats was significantly suppressed by L-propranolol injected i.p. (delta Tmax = 0.14 +/- 0.15 degrees C for L-propranolol vs. 0.78 +/- 0.15 degrees C for vehicle-treated rats). Neither i.p. injection of D-propranolol nor nadolol had any effect on the increase in Tb induced by exposure to the open field. Both i.c.v. doses of L-propranolol and nadolol markedly attenuated the open field-induced rise in Tb. The large i.c.v. dose of D-propranolol (50 micrograms) did, whereas the lower dose (5 micrograms) did not suppress the elevation in Tb in open field exposed rats. The open field-exposed rats injected with L-propranolol (both i.p. or i.c.v.) had lower plasma IL-6 activity than that of open field-exposed rats injected with vehicle (for i.p. injection: 5.2 +/- 1.3 U/ml for L-propranolol vs. 17.4 +/- 3.8 U/ml for vehicle; for i.c.v. injection: 3.5 +/- 2.3 U/ml for L-propranolol vs. 24.4 +/- 7.2 U/ml for vehicle). Nadolol blocked the open field-induced rise in plasma IL-6 only when injected i.c.v. but no i.p. Neither i.p. nor i.c.v. D-propranolol injection had an effect on plasma IL-6 activity in open field-exposed rats. These data show that beta-adrenoceptors in the central nervous system are involved in the psychological stress-induced elevation in Tb and rise in plasma IL-6 activity caused by exposure to an open field.

Adrenergic beta-Antagonists↗
PubMed1995

Resistance to fever induction and impaired acute-phase response in interleukin-1 beta-deficient mice.

We used gene targeting in embryonic stem cells to introduce an IL-1 beta null allele in mice. The IL-1 beta-deficient mice develop normally and are apparently healthy and fertile. The IL-1 beta null mice responded normally in models of contact and delayed-type hypersensitivity or following bacterial endotoxin LPS-induced inflammation. The IL-1 beta-deficient mice showed equivalent resistance to Listeria monocytogenes compared with wild-type controls. In contrast, when challenged with turpentine, which causes localized inflammation and tissue injury, the IL-1 beta mutant mice exhibited an impaired acute-phase inflammatory response and were completely resistant to fever development and anorexia. These results highlight a central role for IL-1 beta as a pyrogen and a mediator of the acute-phase response in a subset of inflammatory disease models, and support the notion that blocking the action of a single key cytokine can alter the course of specific immune and inflammatory responses.

Acute-Phase Reaction↗
PubMed1995

Thermal and behavioral effects of lipopolysaccharide and influenza in interleukin-1 beta-deficient mice.

This study characterized body temperature (Tb), locomotor activity (Act), and feeding behavior under normal conditions and following injection with lipopolysaccharide (LPS) or inoculation with live influenza virus of transgenic C57/black mice deficient in interleukin-1 beta (IL-1 beta). Tb and Act in freely moving mice were measured by biotelemetry. Mice deficient in IL-1 beta had normal circadian rhythm of Tb but were less active than their control counterparts. Mice injected with LPS (2.5 mg/kg i.p.) responded with a prompt decrease of Tb, which lasted approximately 10 h, followed by a fever in which Tb reached a peak at approximately 24 h postinjection. There was no difference between groups in the early drop of Tb after the LPS; however, the 24-h peak of Tb was lower in IL-1 beta-deficient mice. The anorexic effects of LPS and influenza infection were similar in both groups of mice. In mice given influenza virus (17.5 plaque-forming units, median lethal dose), Tb and Act gradually decreased. The fall of Tb was smaller in the transgenic mice. The mice deficient in IL-1 beta displayed a higher mortality rate due to influenza infection than the control mice. We conclude that deficiency in IL-1 beta results in lower fever following the LPS injection and in impairment of the defense response to infection with influenza.

Animals↗
PubMed1993

Secretogranin II: regulation of synthesis and post-translational proteolysis in bovine adrenal chromaffin cells.

Secretogranin II (SgII), also called chromogranin C, is an acidic tyrosine-sulfated secretory protein found in secretory granules in a wide variety of endocrine cells and neurones. Although less abundant than chromogranin A (CGA) and chromogranin B (CGB), SgII is found in adrenal medullary chromaffin granules. In the present study we investigated the regulation of SgII biosynthesis in bovine chromaffin cells maintained in primary culture. Cellular proteins were labelled with [35S]methionine and the heat stable chromogranin enriched fraction was isolated. Following electrophoretic separation, the 86 kDa SgII band was identified by sequence analysis using the Edman degradation procedure. The radioactivity incorporated in the 86 kDa SgII band was used as an index of the SgII synthesis rate. We found that stimulation of chromaffin cells with nicotine and histamine and to a smaller extent with angiotensin II and bradykinin significantly enhanced the rate of SgII synthesis. In contrast direct depolarization with K+ may not be sufficient to induce modifications in SgII synthesis suggesting that the raise of cytosolic calcium evoked by high K+ may not be sufficient to induce modifications in SgII synthesis . The possible second messenger pathways involved in the control of SgII biosynthesis were investigated by using protein kinase C and adenylate cyclase activators. We observed that 12-O-tetradecanoylphorbol 13-acetate (TPA) and forskolin increased the basal rate of SgII synthesis. Incubation with both TPA and forskolin was required to obtain an effect comparable to that produced by nicotine or histamine suggesting that these secretagogues recruit both protein kinase C- and cyclic AMP-dependent mechanisms to stimulate SgII synthesis.

Adenylyl Cyclase Inhibitors↗
PubMed1991

Course of fever response to repeated administration of sublethal doses of lipopolysaccharides, polyinosinic:polycytidylic acid and muramyl dipeptide to rabbits.

The purpose of the present study was to examine the development of tolerance to three structurally dissimilar pyrogens, i.e., lipopolysaccharide (LPS), muramyl dipeptide (MDP) and polyinosinic:polycytidylic acid (poly I:C) in rabbits. The possibility of pyrogenic cross-tolerance among these agents has also been studied. It was observed that repeated injection of sublethal doses of LPS and MDP was connected with the changing of biphasic fever to monophasic. The consequence of this was a drop in the fever index. In contrast to LPS and MDP, the repeated administration of poly I:C did not result in such changes. Successive injections of this pyrogen always evoked biphasic fever. We also demonstrated that pyrogenic cross-tolerance between LPS and MDP did not occur. The cross-tolerance between LPS and MDP did not occur. The cross-tolerance among pyrogens was possible if they originated from the same class, for example endotoxin from Salmonella abortus eq. and endotoxin from Escherichia coli.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Lack of pyrogenic tolerance transmission between brain and periphery in the rabbit.

Successive injections of lipopolysaccharide (LPS) either intravenously (i.v.) or intracerebroventricularly (i.c.v.) induced pyrogenic tolerance to LPS in rabbits. Tolerance was shown by a decrease of the magnitude of the fever response to repeated doses of LPS, irrespective of the route of pyrogen administration. A significantly greater and more dramatic decrease of the fever index, however, was observed in rabbits made tolerant to pyrogen given i.v. than when the pyrogen was given i.c.v. Transmission of the pyrogenic tolerance between brain and peripheral tissues, however, has not been ascertained.

Animals↗
PubMedDate not supplied

Beta-adrenergic receptor subtype effects on stress fever and thermoregulation.

Exposure to psychological stress increases body temperature (Tb). This stress fever may be immunologically beneficial in some patient populations but detrimental in others (e.g., HIV-infected individuals). For this reason, it is desirable to determine pharmacological methods of preventing stress fever. In rats, stress fever is modeled by exposure to a novel environment or 'open field.' The beta-adrenergic antagonists, nadolol and propranolol, block this stress fever. Neither of these beta-antagonists discriminates between subtypes of beta-receptors. The purpose of this study was to determine the relative contribution of the different beta-receptor types to stress fever using beta1-, beta2-, and beta3-receptor subtype selective antagonists (atenolol [beta1], ICI-118551 [beta2], and SR 59230A [beta3]) and agonists (dobutamine [beta1], salbutamol [beta2], and BRL 37344 [beta3]) on the Tb of rats. Tb was measured with a biotelemetry system. Our data suggest that central nervous system beta-receptor blockade with subtype-selective antagonists prevents the stress-induced rise in Tb; however, the beta3-antagonist was effective only at doses that produced hypothermia in a non-stressed control group. The stress-induced fever was mimicked by central nervous system administration of the selective beta2-agonist, salbutamol, and the beta3-agonist, BRL 37344. We hypothesize that the blockade of stress-induced fever by beta-blockers may be due to the sedative actions of these drugs.

Adrenergic beta-Agonists↗