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PubMed2003

Inflammation, the metabolic syndrome and cardiovascular risk.

Over the past ten years it has become clear that cardiovascular disease (CVD) and atherosclerosis have a 'microinflammatory' component and are often associated with low levels of inflammatory markers that are in the upper part of the 'normal' range. In particular, diseases that predispose to CVD, such as the metabolic syndrome and type 2 diabetes, appear to have a very strong inflammatory component. While the inflammatory process is very complicated, single measures, such as C-reactive protein (CRP) or fibrinogen, have clear benefits as they summarise many different parts of the inflammatory process and are easy to apply. However, it is important to remember that the process of inflammation includes coagulation, fibrinolysis, complement activation, antioxidation, immune response and hormonal regulation through the hypothalamic-pituitary-adrenal axis. Furthermore, genetic variation, differences in exposure to environmental influences and the mass of inflammation-producing tissue (e.g. adipose tissue) can all influence responses. Thus, the relationship between atherosclerosis, the metabolic syndrome and inflammation is extraordinarily complex. Inflammatory markers such as CRP exhibit strong CVD-risk prediction that is consistent across sexes and a number of different populations. They reflect risk not only for 'vulnerable plaque' and myocardial infarction (MI) but also for other cardiovascular diseases. In fact, inflammation is associated with several, if not all, of the chronic diseases of old age, and it is now clear that there are important links between inflammation and general metabolism. For instance, visceral adiposity exerts a major influence on inflammation status. Medications that affect atherosclerosis appear to do so at least in part by influencing inflammation (for instance, the emerging pleiotropic effects of statins), and this has far-reaching ramifications for chronic diseases of old age and their treatment.

Arteriosclerosis↗
PubMedDate not supplied

Does evidence of inflammation on Papanicolaou smears of pregnant women predict preterm labor and delivery?

BACKGROUND: Preterm delivery is the most common cause of neonatal morbidity and mortality in the United States. There is evidence that cervicovaginal infection could predispose to preterm labor. This study explored a possible association of evidence of inflammation on an otherwise normal Papanicolaou smear obtained during pregnancy with subsequent preterm labor and preterm delivery. METHODS: Using a retrospective matched cohort design, we studied women who gave birth to live singleton infants at the University of Missouri Hospital and Clinics during a 21-month period. Papanicolaou smears were obtained from 1 to 8 months before delivery and were interpreted in the same cytopathology laboratory. Data pertaining to outcome variables and potential confounding variables were collected from hospital charts. RESULTS: Incidence rates were 14.4 percent for labor < 37 weeks' gestation (preterm labor), 12.3 percent for hospitalization for preterm labor, 9.9 percent for delivery < 37 weeks (preterm delivery), 2.6 percent for delivery < 34 weeks, and 7.5 percent for birth weight < 2500 g. On univariate and multivariate analyses, there were no significant differences in any outcome between the 293 women with inflammation and the 284 women without inflammation on Papanicolaou smear. Results were unchanged when the analysis was limited to the 412 women who received no antibiotics during pregnancy. Among the 38 women with a history of preterm labor or preterm delivery, those with cervical inflammation had a higher rate of preterm labor than those without inflammation. CONCLUSIONS: In the sample as a whole, there was little evidence that findings of inflammation on Papanicolaou smear constituted a risk factor for preterm labor or preterm delivery. The data suggest that inflammation could be associated with an increased risk in a subgroup of women at higher risk by virtue of their obstetric history.

Adult↗
PubMed1992

Augmentation of intraocular inflammation by melanin.

The inflammatory response in endogenous uveitis or after anterior segment surgery was noted to be substantially greater in heavily pigmented eyes. Because varying amounts of melanin are released into the anterior chamber after intraocular inflammation, it was hypothesized that a proinflammatory effect of melanin might account for the enhanced inflammatory response in these eyes. To test this hypothesis, albino (BALB/c) or pigmented (C57BL/6) mice were challenged in the anterior chamber 2 weeks after a subcutaneous foot pad injection of horse serum or conalbumin dissolved in Freund's complete adjuvant. The degree of inflammation in the challenged eyes was determined by histologic examination 72 hr after the challenge. In all cases, the inflammatory infiltrate consisted mainly of polymorphonuclear leukocytes suggestive of an Arthus reaction. An anterior chamber challenge of horse serum-sensitized BALB/c or C57BL/6 mice with horse serum alone resulted in mild inflammation, which was augmented markedly by challenge with a combination of horse serum and melanin. The presence of melanin in the anterior chamber similarly increased the inflammatory response of conalbumin-sensitized mice to anterior chamber challenge with conalbumin. Melanin in the anterior chamber also significantly (P less than 0.05) augmented the inflammatory response of conalbumin-sensitized mice to a horse serum challenge, but it did not significantly augment the inflammatory response of horse serum-sensitized mice to a conalbumin challenge. The heterologous antigens induced minimal inflammation in the absence of melanin. Injection of melanin alone did not evoke an inflammatory response. Ocular challenge with melanin alone or in combination with antigen induced minimal inflammation in nonsensitized mice. However, preincubation of melanin with sera from horse serum-sensitized mice significantly increased its proinflammatory capacity when injected with horse serum into the anterior chamber of nonsensitized mice. In vitro binding studies using fluorescein isothiocyanate-conjugated mouse immunoglobulin G showed a high binding capacity of melanin for immunoglobulin G. It was concluded that the presence of free melanin in the anterior chamber can increase intraocular inflammation. Although the mechanism(s) by which melanin augments inflammation has not been defined, these data suggest that the binding of serum components (such as antibodies) to melanin may contribute to its proinflammatory effect.

Albinism↗
PubMed1991

The intratracheal administration of endotoxin and cytokines. III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation.

Endotoxin, a lipopolysaccharide (LPS) component of gram-negative bacteria, induces alveolar macrophages to express interleukin-1 (IL-1). Lipopolysaccharide and IL-1 both cause severe acute neutrophilic inflammation in the lung after intratracheal injection, suggesting that LPS-induced IL-1 expression contributes to the pathogenesis of LPS-induced acute inflammation. In the present study, the role of IL-1 in LPS-induced acute pneumonia was investigated by quantitating the acute inflammation occurring at 6 hours after the intratracheal injection of LPS as compared to the same timepoint after the intratracheal coinjection of LPS and IL-1 receptor antagonist (IL-1ra). The IL-1ra was found to inhibit LPS-induced acute inflammation (P greater than 0.0001) as measured by the number of neutrophils recovered in bronchoalveolar lavage. The LPS-induced emigration of neutrophils was inhibited by as much as 45%. Recombinant IL-1 beta-induced neutrophil emigration into the lung was inhibited by 95% when IL-1ra was coinjected intratracheally with IL-1 beta. Coinjection of recombinant IL-1 beta and LPS increased the neutrophilic exodus as compared to the intratracheal injection of either agent alone. Intratracheal injection of LPS induces a progressive increase in IL-1ra mRNA expression in whole-lung RNA preparations, suggesting that endogenous IL-1ra may play an important role as a negative feedback mechanism to downregulate LPS initiated IL-1-mediated acute inflammation. In conclusion IL-1ra inhibits both LPS- and IL-1-induced neutrophilic inflammation and may therefore prove clinically useful as an anti-inflammatory agent for the therapy of either septic or aseptic IL-1-mediated acute inflammation.

Animals↗
PubMedDate not supplied

[Epidemiologic characteristics of acute and recurrent middle ear inflammation in childhood].

The authors studied the incidence of acute and relapsing inflammations of the middle ear, together with factors relating to inflammation in 393 children aged up to 36 months. The results revealed that of 393 children followed up for 12 months, 175 (44.52%) had acute otitis media and 40 (22.85%) had relapses. No relationship was found between age and acute inflammation, but the rate of relapses was significantly higher during the first year of life. There was no significant influence of the sex of the child, socioeconomic status and place of living on the appearance of the inflammations. The attendance of infant nurseries and day-care centres had significant influence on higher rate of acute inflammations but not on relapses. There was no influence of acute otitis media of the members of the family on incidence of the same disease in their children, but there was evidence of influence on relapses. The highest incidence of inflammation occurred in autumn and winter months, November, December and January (61.67%) versus only 1.76% in summer months (July, August). Only 2 children had scars of the eardrums presenting as an early consequence of the disease, while none had any complications of the middle ear inflammation.

Acute Disease↗
PubMed1986

Pulmonary inflammation in autoimmune MRL/Mp-lpr/lpr mice. Histopathology and bronchoalveolar lavage evaluation.

Early detection of lupus pneumonitis is difficult because it requires lung biopsy. The authors describe here in detail the age-related histologic changes in pulmonary inflammation, the age-related changes in bronchoalveolar lavage (BAL), and the effect of cyclophosphamide (8 mg/kg) on pulmonary inflammation and bronchoalveolar lavage in MRL/Mp-lpr/lpr mouse, an animal model of systemic lupus erythematosus. To assess the evolution of pulmonary inflammation and response to cyclophosphamide therapy, they compared the age-related progression of pulmonary inflammation with sequential changes in BAL cell populations in this autoimmune mouse model. A striking similarity was noted between age-related changes in pulmonary inflammation and lymphocyte counts in BAL. A trend to reduction in histologic evidence of inflammation was reflected by lymphocytes in BAL in cyclophosphamide-treated (8 mg/kg/day) males but not in females. There was a striking sex-related difference in that the histologic evidence of pulmonary inflammation and bronchoalveolar lavage lymphocyte count in cyclophosphamide-treated males was significantly lower than cyclophosphamide-treated females of the same age.

Aging↗
PubMed1983

[Action of piroxicam on allergic inflammation].

Effects of piroxicam on allergic inflammation were investigated with allergic air pouch inflammation and antigen-induced arthritis in rats. In allergic air pouch inflammation, piroxicam exerted a dose-dependent inhibition (1-10 mg/kg, p.o.) of the exudate production, the migration of leukocytes and the release of lysosomal enzyme into the exudate; and its potency was superior to that of indomethacin and equivalent to that observed with prednisolone. In contrast with this, the suppressive effect of piroxicam on non-allergic air pouch inflammation was as weak as indomethacin. Prednisolone showed a similar effect on both types of air pouch inflammation. In antigen-induced arthritis, piroxicam showed a dose-dependent (0.3-3 mg/kg, p.o.) inhibitory effect on knee joint swelling and an improving action on the functional disorder of the inflamed joint. On this model, piroxicam was 3 to 4 times more active than both indomethacin and prednisolone. In non-allergic joint inflammation induced with croton oil in rats, however, the anti-inflammatory potency of piroxicam was almost equal to those of indomethacin and prednisolone. Piroxicam showed more potent inhibition than indomethacin on heterologous passive cutaneous anaphylaxis in rats, but showed only a slight inhibition on the increased vascular permeability caused by histamine and bradykinin. Piroxicam had no influence upon the plaque-forming cell response and the delayed hypersensitivity reaction in mice; furthermore, the hemolytic activity of complement in guinea-pig serum was scarcely affected by piroxicam in vitro. These results indicate that piroxicam possesses prominent efficiency on allergic inflammation and may function on several activities of inflammatory cells.

Air Sacs↗
PubMed1995

Expression of epithelial adhesion proteins and integrins in chronic inflammation.

Epithelial cell behavior in chronic inflammation is poorly characterized. During inflammation of tooth-supporting structures (periodontal disease), increased proliferation of epithelial cells into the inflamed connective tissue stroma is commonly seen. In some areas ulceration and degeneration take place. We studied alterations in the expression of adhesion molecules and integrins during chronic periodontal inflammation. In inflamed tissue, laminin-1 and type IV collagen were still present in the basement membrane and surrounding blood vessels, but they were also found extravascularly in inflamed connective tissue stroma. Type VII collagen and laminin-5 (also known as kalinin, epiligrin, or nicein) were poorly preserved in the basement membrane zone, but both were found in unusual streak-like distributions in the subepithelial connective tissue stroma in inflamed tissue. Both fibronectin and tenascin were substantially decreased in chronically inflamed connective tissue, showing only punctate staining at the basement membrane zone. Integrins of the beta 1 family showed two distinct staining patterns in epithelial cells during chronic inflammation; focal losses of beta 1 integrins (alpha 2 beta 1 and alpha 3 beta 1) were found in most areas, while in other areas the entire pocket epithelium was found to be strongly positive for beta 1 integrins. No members of the alpha v integrin family were found in any epithelia studied. Expression of the alpha 6 beta 4 integrin was high in basal cells of healthy tissue, but weak in epithelium associated with chronic inflammation. Chronic inflammation therefore involves alterations in both adhesion proteins and integrins expressed by epithelial cells. Basement membrane components found at abnormal sites in stroma in chronic inflammation might serve as new adhesive ligands for various cell types in inflamed stroma.

Antibodies, Monoclonal↗
PubMedDate not supplied

Cervical inflammation and preterm delivery in pregnant women with a history of preterm delivery.

BACKGROUND: A previous preterm delivery is a risk factor for preterm delivery in a subsequent pregnancy. We tested the hypothesis that evidence of inflammation on a Papanicolaou smear obtained during pregnancy is a risk factor for preterm delivery for women with a history of preterm delivery. METHODS: We studied women who had two singleton deliveries at a university hospital during an 8-year period. Women eligible for our study were those whose first delivery was preterm (< 37 weeks of gestation) and for whom a Papanicolaou smear was obtained during the second pregnancy. These smears were examined for evidence of inflammation by a cytopathologist. Information about the second pregnancy was obtained by chart review. RESULTS: The cytopathologist reviewed Papanicolaou smears from 92 study pregnancies and found evidence of cervical inflammation on 34 smears (37 percent). Preterm delivery ended 24 (26.1 percent) of the second pregnancies. The incidence of preterm delivery in women with inflammation on Papanicolaou smear was 41.2 percent compared with an incidence of 17.2 percent in women without inflammation (relative risk of 2.40 with a 95 percent confidence interval of 1.19 to 4.83). This association remained significant after controlling for potential confounding variables. A stratified analysis found that the association of cervical inflammation with preterm delivery was limited to women who had systemic exposure to an antibiotic during pregnancy. CONCLUSION: Among pregnant women with a history of preterm delivery, evidence of inflammation on Papanicolaou smear was associated with an increased risk of preterm delivery. If replicated in other studies, this finding might have implications for the management of pregnancies in women with a history of preterm delivery.

Adult↗
PubMed1996

Effects of ursodeoxycholic acid on hepatic inflammation and histological stage in patients with primary biliary cirrhosis.

OBJECTIVES: Ursodeoxycholic acid (UDCA) has been reported to be of benefit in the treatment of primary biliary cirrhosis; however, the effects of UDCA on the histological features of primary biliary cirrhosis are uncertain. The goal of this study was to determine the histological effects of 2 yr of treatment with UDCA compared to placebo in a prospective randomized trial of primary biliary cirrhosis. We also sought to correlate the changes in inflammation and histological stage with changes in serum bilirubin, Mayo Risk Score, and the percentage of UDCA in bile in these patients. METHODS: Sixty-one patients (32 receiving UDCA, 29 receiving placebo) who had initial and 2-yr biopsies were studied. Biopsy specimens were evaluated by a single pathologist under coded identification. The degree of inflammation and histological stage were graded on a scale of 0 to 4. RESULTS: There was no significant difference in the degree of inflammation with UDCA treatment when compared to the placebo group at 2 yr. There was a significant but weak indirect association between degree of enrichment of UDCA and changes in inflammation (r = -0.34, p = .02). There was no detectable change in stage in either the UDCA-treated or placebo group when comparing pre- and posttreatment specimens. There were no associations with changes in serum bilirubin or Mayo Risk Score and degree of inflammation. CONCLUSIONS: No significant changes in the degree of inflammation or histological stage were apparent after 2 yr of treatment with UDCA or in the placebo group. A tendency toward improvement in inflammation was noted with greater degrees of biliary UDCA enrichment. Longer term studies will be necessary to determine whether UDCA has a beneficial effect on histological stage.

Bilirubin↗
PubMed1996

[Effects pf captopril and D-penicillamine on kinins-mediated and chronic inflammation].

In our study the effects of angiotension converting enzyme inhibitor captopril and immunosuppressant agent d-penicillamine were investigated on inflammations mediated by kinins and on adjuvant arthritis in rat paw oedema tests. Kinins mediated inflammations were increased by small doses of captopril (0.04-5 mg/kg per os) in a dose dependent manner. However this effect of captopril was reduced at higher doses of the drug (5-400 mg/kg). In the case of d-penicillamine there was exerted an inflammation increasing effect similarly to captopril. Maximum value of this action could be measured at dose 100 mg/kg per os. After administration higher doses of d-penicillamine were not revealed any depression in inflammation increasing effect. In capillary resistance studies we have shown capillary resistance increasing action of captopril that was dose depend. However this effect was not found in the case of d-penicillamine. According to these finding kinins mediated inflammation increasing effects of captopril and d-penicillamine are suggested as a results of their ability inhibit angiotensin converting enzyme. Maximum depression at higher doses of captopril may be caused by its capillary resistance elevating action. In chronic inflammations studies we have shown developments of secondary symptoms of adjuvant arthritis inhibiting effects of captopril and d-penicillamine in a dose dependent manner. We assume that immunosuppressive action of both drug are responsible for reduction of chronic inflammations. Our study strengthens the argument that captopril can be used in therapy of rheumatoid arthritis. Further clinicopharmacological studies of captopril may clarify the role of this drug in therapy of rheumatoid diseases.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effect of ursodeoxycholic acid on the inflammatory activity of indomethacin-induced intestinal inflammation in rats.

The beneficial effects of ursodeoxycholic acid (UDCA) in primary biliary cirrhosis are supposed to be mediated in part by immunological mechanisms. In this study, we have tested whether ursodeoxycholic acid also ameliorates intestinal inflammation induced by indomethacin in rats. Intestinal inflammation was induced in rats by two injections of indomethacin (7.5 mg/kg body weight) 24 h apart. To study its effects on acute inflammation, UDCA (10 mg/kg body weight) was given for three days starting with the first administration of indomethacin; for effects on chronic inflammation, UDCA was given 24 h after the first indomethacin injection for eight days. Rats were sacrificed at days 3 and 9, respectively. In acute inflammation a significant decrease of intestinal injury was observed with UDCA treatment (macroscopic score: 3.00 +/- 0.83 vs. 6.55 +/- 0.53 in controls; p < 0.01; microscopic score: 1.66 +/- 0.28 vs. 2.89 +/- 0.35 in controls; p < 0.05). In chronic inflammation the effects of UDCA treatment were less marked due to a general decline in intestinal injury. Nevertheless a significant decrease in the macroscopic injury score (3.67 +/- 0.62 vs. 1.55 +/- 0.29 in UDCA treated rats; p < 0.01) was observed. Also, there was a significant increase in body weight of UDCA treated rats after nine days compared to controls (28.8% vs. 16% increased body weight in controls; p < 0.01). Thus, ursodeoxycholic acid attenuates the severity of acute damage of small bowel and the development of chronic intestinal inflammation induced by indomethacin in rats.

Acute Disease↗
PubMed1997

Interleukin-1 mediates guinea pig gallbladder inflammation in vivo.

Interleukin-1 (IL-1) is a cytokine with multiple immunologic and inflammatory properties. We previously demonstrated that lipopolysaccharide (LPS) stimulates release of IL-1, and IL-1 stimulates inflammation in guinea pig gallbladder in vivo. We hypothesized that IL-1 mediates LPS-induced guinea pig gallbladder inflammation in vivo. LPS and IL-1 were instilled into guinea pig gallbladder lumen alone (with cystic duct ligation) and with IL-1 ra and indomethacin, respectively (n = 4). Water transport across gallbladder mucosa, myeloperoxidase and IL-1 release from gallbladder tissue, and prostaglandin E2 (PGE2) in lumenal fluid were measured. Values for test agents and inhibitory agents were compared to saline controls using Student's t test (P < 0.05). Intralumenal LPS and IL-1 both stimulated gallbladder inflammation. LPS-induced and IL-1-induced inflammation were inhibited by both IL-1 ra and indomethacin. LPS stimulated IL-1 release and IL-1 itself caused gallbladder inflammation. LPS stimulated gallbladder inflammation as manifest by increased myeloperoxidase and PGE2 release, and water secretion into the gallbladder lumen. The inflammatory effects of LPS were inhibited by IL-1 ra. Taken together, these findings indicate that IL-1 is a mediator of LPS-induced guinea pig gallbladder inflammation in vivo.

Animals↗
PubMed1998

Blockade of N- and P/Q-type calcium channels reduces the secondary heat hyperalgesia induced by acute inflammation.

High voltage calcium channels are implicated in nociceptive transmission after nerve injury, capsaicin or formalin injection. The purpose of this study was to investigate the role of calcium channels in secondary heat hyperalgesia associated with acute joint inflammation. After induction of acute inflammation (knee joint injection of kaolin and carrageenan), decreased paw withdrawal latency (PWL) to radiant heat (i.e., secondary heat hyperalgesia), increased guarding of the limb and increased joint circumference occurs. Spinal administration (through a microdialysis fiber placed in dorsal horn) of an N-type calcium channel blocker (MVIIA, SNX 111, ziconotide, 0.001-0.1 mM), before induction of inflammation, prevents the decrease in PWL. Treatment with SNX 111 4 hr after inflammation reverses heat hyperalgesia. A small reduction in spontaneous pain-related behaviors (guarding of the limb) occurs after pre- or post-treatment with SNX 111. Spinal blockade of P/Q-type calcium channels (with omega-agatoxin IVA) had no effect on the decrease in PWL to radiant heat when administered after induction of inflammation. However, pre-treatment with omega-agatoxin IVA prevents secondary heat hyperalgesia. omega-Agatoxin IVA has no effect on spontaneous pain-related behaviors whether administered before or after induction of inflammation. In contrast, pre or post-treatment with nifedipine (L-type calcium channel blocker, 0.01-1.0 mM), had no effect on heat hyperalgesia or spontaneous pain-related behaviors induced by acute inflammation. There were no differences in joint circumference between groups with any treatment. Thus, N-type calcium channels contribute to both the development and maintenance of secondary heat hyperalgesia while P-type calcium channels are only involved during development of hyperalgesia.

Animals↗
PubMed2005

Functional aspects and mechanisms of TRPV1 involvement in neurogenic inflammation that leads to thermal hyperalgesia.

Neurogenic inflammation is produced by overstimulation of peripheral nociceptor terminals by injury or inflammation of tissues. Excessive activity of sensory neurons produces vasodilation, plasma extravasation and hypersensitivity. Mechanistically, neurogenic inflammation is due to the release of substances from primary sensory nerve terminals that act directly or indirectly at the peripheral terminals, either activating or sensitizing nociceptors, endothelial cells and immunocytes. Notably, small-diameter sensory neurons that are sensitive to capsaicin play a key role in the generation of neurogenic inflammation. The cloning of the vanilloid receptor 1 (TRPV1) has been a breakthrough that has propelled our understanding of the molecular mechanisms involved in neurogenic inflammation. TRPV1 pivotally contributes to the integration of various stimuli and modulates nociceptor excitability, thus making it a true gateway for pain transduction. In addition, TRPV1 is the endpoint target of intracellular signalling pathways triggered by inflammatory mediators. Phosphorylation-induced potentiation of TRPV1 channel activity, along with an incremented TRPV1 surface expression are major events underlying the nociceptor activation and sensitization that leads to thermal hyperalgesia. The important contribution of TRPV1 receptor to the onset and maintenance of neurogenic inflammation has validated it as a therapeutic target for inflammatory pain management. As a result, the development of specific TRPV1 antagonists is a central focus of current drug discovery programs.

Animals↗
PubMed2004

Medroxyprogesterone acetate, but not progesterone, protects against inflammation-induced parturition and intrauterine fetal demise.

OBJECTIVE: This study was undertaken to determine whether progestational agents can prevent inflammation-induced preterm parturition and fetal demise. STUDY DESIGN: The activation of contractile and inflammatory pathways in response to localized intrauterine inflammation was investigated by using quantitative polymerase chain reaction (PCR). Serum progesterone (P4) levels and alterations in progesterone receptor-B (PR-B) were determined with radioimmunoassay and quantitative PCR, respectively. With our in vivo model of intrauterine inflammation, animals were randomly assigned to pretreatment with P4 or medroxyprogesterone acetate (MPA) before intrauterine lipopolysaccharide (LPS). Animals were observed for preterm delivery. The number of live pups 48 hours after intrauterine LPS was recorded for each treatment group. The ability of MPA to alter signal transduction pathways leading to preterm parturition were investigated by quantitative PCR and histochemical studies. RESULTS: Intrauterine inflammation is associated with decreased serum progesterone levels and decreased transcription of PR-B. Preterm delivery rates were 100% for LPS alone, 63% for LPS+P4, and 0% for LPS+MPA. No live pups remained at 48 hours in the LPS or LPS+P4 groups. Pretreatment with MPA significantly preserved fetal viability. MPA suppressed activation of contraction-associated genes and inflammatory mediators and prevented cervical ripening in response to intrauterine inflammation. CONCLUSION: MPA, with its progestational and anti-inflammatory properties, prevented inflammation-induced preterm parturition and significantly preserved fetal viability.

Animals↗
PubMed2001

Concurrent inflammation as a determinant of susceptibility to toxicity from xenobiotic agents.

Sensitivity to the toxic effects of xenobiotic agents is influenced by a number of factors. Recent evidence derived from studies using experimental animals suggests that inflammation is one of these factors. For example, induction of inflammation by coexposure to bacterial endotoxin, vitamin A or Corynebacterium parvum increases injury in response to a number of xenobiotic agents that target liver. These agents are diverse in chemical nature and in mechanism of hepatotoxic action. Factors critical to the augmentation of liver injury by inflammation include Kupffer cells, neutrophils, cytokines such as tumor necrosis factor-alpha (TNF-alpha) and lipid mediators such as prostaglandins, but these may vary depending on the xenobiotic agent and the mechanisms by which it alters hepatocellular homeostasis. In addition, the timing of inflammagen exposure can qualitatively alter the toxic response to chemicals. Inflammation-induced increases in susceptibility to toxicity are not limited to liver. Concurrent inflammation also sensitizes animals to the toxic effects of agents that damage the respiratory tract, kidney and lymphoid tissue. It is concluded that inflammation should be considered as a determinant of susceptibility to intoxication by xenobiotic exposure.

Animals↗
PubMed2003

Targeting G protein-coupled A2a adenosine receptors to engineer inflammation in vivo.

G protein-coupled adenosine receptors are the subject of intense study as immunomodulators of inflammation especially since the recent demonstration that the A2a receptor acts to down-regulate inflammation and inhibit tissue damage in vivo [Nature 414 (6866) (2001) 916]. The adverse effects of overactive inflammation are evident in diseases e.g. sepsis, rheumatoid arthritis, and multiple sclerosis underscoring the importance of inhibiting inflammation or selectively enhancing inflammatory processes. It has been shown recently that the A2a adenosine receptor is a critical component of an endogenous "immunosuppressive loop" in which extracellular adenosine that accumulates due to local hypoxia caused by inflammatory insult signals through cAMP-elevating A2a receptors in a delayed negative feedback manner. Understanding how tissues regulate inflammation will provide the information necessary to allow for the engineering, or selective targeting, of endogenous inflammatory pathways. Recognition of A2a receptors as "natural" or endogenous brakes of inflammation provides the intellectual scaffolding needed to pursue these goals.

Animals↗