Degree Of Tissue Inflammation Research Articles

Fast hypothermia induced by extracorporeal circuit cooling alleviates renal and intestinal injury after cardiac arrest in swine.

Continuous renal replacement therapy (CRRT) was currently demonstrated to be an effective way to induce fast hypothermia and had proective effects on cardiac dysfunction and brain damage after cardiac pulmonary resuscitation (CPR). In the present study, we aimed to investigate the influence of extracorporeal circuit cooling using CRRT on renal and intestinal damage after CPR based on a porcine model. 32 pigs were subjected to ventricular fibrillation for 8 min, followed by CPR for 5 min before defibrillation. All were randomized to receive extracorporeal circuit cooling using CRRT (CRRT, n = 9), surface cooling (SC, n = 9), normothermia (NT, n = 9) or sham control (n = 5) at 5 min post resuscitation. Pigs in the CRRT group were cooled by 8-h CRRT cooling with the infusion line initially submerged in 4 °C of ice water and 16-h SC, while in the SC group by a 24-h SC. Temperatures were maintained at a normal range in the other two groups. Biomarkers in serum were measured at baseline and 1, 3, 6, 12, 24 and 30 h post resuscitation to assess organ functions. Additionally, tissues of kidney and intestine were harvested, from which the degree of tissue inflammation, oxidative stress, and apoptosis levels were analyzed. The blood temperature decreased faster by extracorporeal circuit cooling using CRRT than SC (9.8 ± 1.6 vs. 1.5 ± 0.4 °C/h, P < 0.01). Post-resuscitation renal and intestinal injury were significantly improved in the 2 hypothermic groups compared to the NT group. And the improvement was significantly greater in animals received extracorporeal circuit cooling than those received surface cooling, from both the results of biomarkers in serum and pathological evidence. Fast hypothermia induced by extracorporeal circuit cooling was superior to. surface cooling in mitigating renal and intestinal injury post resuscitation.

CURCUMA LONGA L. HAS THERAPEUTIC EFFECT IN CHEMOTHERAPY-INDUCED ORAL MUCOSITIS IN HAMSTERS DECREASING ANGIOGENESIS AND TRANSFORMING GROWTH FACTOR-β1

Objectives We explored the effects of mucoadhesive formulation with Curcuma longa L. extract (MCL) on oral mucositis induced by 5-fluorouracil in hamsters. Study Design Seventy-two golden Syrian hamsters separated into 4 groups: control group, placebo group (no active substance), positive control group (AdMuc topical chamomile), and MCL group (topical use of mucoadhesive Curcuma longa). The animals received an intraperitoneal injection of 5-fluorouracil on days 0 and 2. On days 3 and 4, the buccal mucosa was scratched, and therapy was initiated on day 5. The animals received 2 daily applications of the product according to the experimental group. Wound area was calculated and histologic sections of 3 μm were stained by hematoxylin and eosin for semiquantitative analysis of re-epithelization and degree of tissue inflammation. Immunohistochemistry was used for transforming growth factor β1 (TGF-β1) and CD31 analysis. Results The MCL group showed a greater clinical reduction of the mucositis lesions at day 8, a higher degree of re-epithelization, and a lower inflammatory process, with a lower angiogenesis and TGF-β1 epithelial labeling compared with the placebo and control groups (P Conclusions MCL Curcuma longa L. has a therapeutic effect accelerating the healing of oral mucositis reducing the inflammatory response and increasing re-epithelization.

Effects of a Portable Peritoneal Lavage Device on Dogs with Seawater-Immersed Open Abdominal Injury

Background Seawater-immersed open abdominal injury is a special injury during marine activities. Effective warmed peritoneal lavage in the field early after injury is the key to treatment. This pilot study aimed at exploring the treatment effects of a self-developed portable peritoneal lavage device compared with conventional treatment model. Material and Methods Beagle dogs were used to develop models of seawater-immersed open abdominal injury. A conventional lavage method or a novel peritoneal lavage device was used for lavage and rewarming. The vital signs, electrolyte, serum inflammatory cytokine expression levels, histological changes of mucosa, and microstructure variety of different groups were observed and compared before and after immersion and 2 h, 1 d, 3 d, and 5 d after lavage. Results The levels of TNF-α, IL-1β, IL-8, IFN-γ, VEGF, and TGF-β in the blood and the damage of tissues and cells in three groups were increased after immersion and decreased at the later points of time after lavage. The concentration of Na+, K+, Cl−, lactate, and lactate dehydrogenase in the plasma was significantly higher than that before immersion (P < 0.05), and the concentration of Ca2+ and HCO3− and plasma pH decreased slightly (P < 0.05). The degree of tissue inflammation and mucosal injury in the delayed control group and device group was lower than the control group. Conclusions Timely lavage and rewarming using a portable peritoneal lavage device reduced the inflammatory response of seawater-immersed open abdominal injury dogs and reduced the damage of multiple organs. The dogs recovered better and faster than the conventional treatment group.

Gp96 Peptide Antagonist gp96-II Confers Therapeutic Effects in Murine Intestinal Inflammation.

The expression of heat shock protein gp96 is strongly correlated with the degree of tissue inflammation in ulcerative colitis and Crohn's disease, thereby leading us to the hypothesis that inhibition of expression via gp96-II peptide prevents intestinal inflammation. We employed daily injections of gp96-II peptide in two murine models of intestinal inflammation, the first resulting from five daily injections of IL-12/IL-18, the second via a single intrarectal application of TNBS (2,4,6-trinitrobenzenesulfonic acid). We also assessed the effectiveness of gp96-II peptide in murine and human primary cell culture. In the IL-12/IL-18 model, all gp96-II peptide-treated animals survived until day 5, whereas 80% of placebo-injected animals died. gp96-II peptide reduced IL-12/IL-18-induced plasma IFNγ by 89%, IL-1β by 63%, IL-6 by 43% and tumor necrosis factor (TNF) by 70% compared to controls. The clinical assessment Disease Activity Index of intestinal inflammation severity was found to be significantly lower in the gp96-II-treated animals when compared to vehicle-injected mice. gp96-II peptide treatment in the TNBS model limited weight loss to 5% on day 7 compared with prednisolone treatment, whereas placebo-treated animals suffered a 20% weight loss. Histological disease severity was reduced equally by prednisolone (by 40%) and gp96-II peptide (35%). Mice treated with either gp96-II peptide or prednisolone exhibited improved endoscopic scores compared with vehicle-treated control mice: vascularity, fibrin, granularity, and translucency scores were reduced by up to 49% by prednisolone and by up to 30% by gp96-II peptide. In vitro, gp96-II peptide reduced TLR2-, TLR4- and IL-12/IL-18-induced cytokine expression in murine splenocytes, with declines in constitutive IL-6 (54%), lipopolysaccharide-induced TNF (48%), IL-6 (81%) and in Staphylococcus epidermidis-induced TNF (67%) and IL-6 (81%), as well as IL-12/IL-18-induced IFNγ (75%). gp96-II peptide reduced IL-1β, IL-6, TNF and GM-CSF in human peripheral blood mononuclear cells to a similar degree without affecting cell viability, whereas RANTES, IL-25 and MIF were twofold to threefold increased. gp96-II peptide protects against murine intestinal inflammation by regulating inflammation in vivo and in vitro, pointing to its promise as a novel treatment for inflammatory bowel disease.

Resident Microbiome Disruption with Antibiotics Enhances Virulence of a Colonizing Pathogen

There is growing evidence that symbiotic microbes play key roles in host defense, but less is known about how symbiotic microbes mediate pathogen-induced damage to hosts. Here, we use a natural wildlife disease system, house finches and the conjunctival bacterial pathogen Mycoplasma gallisepticum (MG), to experimentally examine the impact of the ocular microbiome on host damage and pathogen virulence factors during infection. We disrupted the ocular bacterial community of healthy finches using an antibiotic that MG is intrinsically resistant to, then inoculated antibiotic- and sham-treated birds with MG. House finches with antibiotic-disrupted ocular microbiomes had more severe MG-induced conjunctival inflammation than birds with unaltered microbiomes, even after accounting for differences in conjunctival MG load. Furthermore, MG cultures from finches with disrupted microbiomes had increased sialidase enzyme and cytadherence activity, traits associated with enhanced virulence in Mycoplasmas, relative to isolates from sham-treated birds. Variation in sialidase activity and cytadherence among isolates was tightly linked with degree of tissue inflammation in hosts, supporting the consideration of these traits as virulence factors in this system. Overall, our results suggest that microbial dysbiosis can result in enhanced virulence of colonizing pathogens, with critical implications for the health of wildlife, domestic animals, and humans.

NADPH Oxidase Contributes to Resistance against Aggregatibacter actinomycetemcomitans-Induced Periodontitis in Mice.

Aggregatibacter actinomycetemcomitans is a Gram-negative commensal bacterium of the oral cavity which has been associated with the pathogenesis of periodontitis with severe alveolar bone destruction. The role of host factors such as reactive oxygen and nitrogen intermediates in periodontal A. actinomycetemcomitans infection and progression to periodontitis is still ill-defined. Therefore, this study aimed to analyze the role of NADPH oxidase and inducible nitric oxide synthase (iNOS) in a murine model of A. actinomycetemcomitans-induced periodontitis. NADPH oxidase-deficient (gp91phox knockout [KO]), iNOS-deficient (iNOS KO), and C57BL/6 wild-type mice were orally infected with A. actinomycetemcomitans and analyzed for bacterial colonization at various time points. Alveolar bone mineral density and alveolar bone volume were quantified by three-dimensional micro-computed tomography, and the degree of tissue inflammation was calculated by histological analyses. At 5 weeks after infection, A. actinomycetemcomitans persisted at significantly higher levels in the murine oral cavities of infected gp91phox KO mice than in those of iNOS KO and C57BL/6 mice. Concomitantly, alveolar bone mineral density was significantly lower in all three infected groups than in uninfected controls, but with the highest loss of bone density in infected gp91phox KO mice. Only infected gp91phox KO mice revealed significant loss of alveolar bone volume and enhanced inflammatory cell infiltration, as well as an increased number of osteoclasts. Our results indicate that NADPH oxidase is important to control A. actinomycetemcomitans infection in the murine oral cavity and to prevent subsequent alveolar bone destruction and osteoclastogenesis.

Immunohistochemical Studies on Galectin Expression in Colectomised Patients with Ulcerative Colitis.

Introduction. The aetiology and pathogenesis of ulcerative colitis (UC) are essentially unknown. Galectins are carbohydrate-binding lectins involved in a large number of physiological and pathophysiological processes. Little is known about the role of galectins in human UC. In this immunohistochemical exploratory study, both epithelial and inflammatory cell galectin expression were studied in patients with a thoroughly documented clinical history and were correlated with inflammatory activity. Material and Methods. Surgical whole intestinal wall colon specimens from UC patients (n = 22) and controls (n = 10) were studied. Clinical history, pharmacological treatment, and modified Mayo-score were recorded. Tissue inflammation was graded, and sections were stained with antibodies recognizing galectin-1, galectin-2, galectin-3, and galectin-4. Results. Galectin-1 was undetectable in normal and UC colonic epithelium, while galectin-2, galectin-3, and galectin-4 were strongly expressed. A tendency towards diminished epithelial expression with increased inflammatory grade for galectin-2, galectin-3, and galectin-4 was also found. In the inflammatory cells, a strong expression of galectin-2 and a weak expression of galectin-3 were seen. No clear-cut correlation between epithelial galectin expression and severity of the disease was found. Conclusion. Galectin expression in patients with UC seems to be more dependent on disease focality and individual variation than on degree of tissue inflammation.

Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis.

IntroductionThe functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles.MethodsSynovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro.ResultsScreening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-α, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets.ConclusionsSynovial ELN in RA is strongly associated with activation of the IL-23 pathway but not with IL-17A.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0688-0) contains supplementary material, which is available to authorized users.

Neutrophil Extracellular Traps in Ulcerative Colitis: A Proteome Analysis of Intestinal Biopsies.

The etiology of the inflammatory bowel diseases, including ulcerative colitis (UC), remains incompletely explained. We hypothesized that an analysis of the UC colon proteome could reveal novel insights into the disease etiology. Mucosal colon biopsies were taken by endoscopy from noninflamed tissue of 10 patients with UC and 10 controls. The biopsies were either snap-frozen for protein analysis or prepared for histology. The protein content of the biopsies was characterized by high-throughput gel-free quantitative proteomics, and biopsy histology was analyzed by light microscopy and confocal microscopy. We identified and quantified 5711 different proteins with proteomics. The abundance of the proteins calprotectin and lactotransferrin in the tissue correlated with the degree of tissue inflammation as determined by histology. However, fecal calprotectin did not correlate. Forty-six proteins were measured with a statistically significant differences in abundances between the UC colon tissue and controls. Eleven of the proteins with increased abundances in the UC biopsies were associated with neutrophils and neutrophil extracellular traps. The findings were validated by microscopy, where an increased abundance of neutrophils and the presence of neutrophil extracellular traps by extracellular DNA present in the UC colon tissue were confirmed. Neutrophils, induced neutrophil extracellular traps, and several proteins that play a part in innate immunity are all increased in abundance in the morphologically normal colon mucosa from patients with UC. The increased abundance of these antimicrobial compounds points to the stimulation of the innate immune system in the etiology of UC.

OP0107 Ectopic Lymphoid Neogenesis is Specifically Associated with Activation of the IL-23/IL-17 Pathway in Rheumatoid Synovitis

ObjectivesEctopic lymphoid neogenesis (ELN) occurs in 30-50% of the rheumatoid synovial samples but its functional relevance remains unknown. As ELN correlates with the degree of tissue inflammation we investigated here...

Central pain mechanisms in the rheumatic diseases: future directions.

Pain is a prominent component of many rheumatologic conditions, and is the result of a complex physiologic interaction of central and peripheral nervous system signaling that results in a highly individualized symptom complex. Pain is frequently categorized as acute or chronic (generally greater than three months duration). Chronic pain is not simply acute pain that has lasted longer, and is more likely to be influenced by input from the central nervous system, whereas acute pain is often attributable primarily to inflammation and/or damage in peripheral structures (i.e., nociceptive input). The prominent role of central factors in chronic pain is highlighted by the fact that there is currently no chronic pain condition in which the degree of tissue inflammation or damage alone (e.g., as measured by radiographs, magnetic resonance imaging (MRI), or endoscopy) accurately predicts the presence or severity of pain. Central factors alter pain processing by setting the “gain”, such that when peripheral input is present, it is processed against a background of central factors that can enhance or diminish the experience of pain. There are very large inter-individual differences in these central nervous system factors that influence pain perception, such that some individuals with significant peripheral nociceptive input (e.g. from joint damage or inflammation) will feel little or no pain, whereas others are very pain sensitive, and they can experience pain with minimal or no identifiable abnormal peripheral nociceptive input. This emerging knowledge has important implications for pain management in individuals with chronic rheumatologic disorders.

Lasers in Periodontics- A dilemma

With the development of the first laser by Mainam in 1960, over decades, the subject has grown by leaps and bounds in dentistry over the conventional therapies. However, despite a large number of studies, the application of lasers for the treatment of periodontitis remains controversial. Lasers used today are either a continuous, pulsed (gated) or running pulse waveform. E.g. CO2, Nd:YAG, Ho:YAG, Er:YAG, Er,Cr:YSGG, Nd:YAP, GaAs(diode) and Argon. Two main factors that determine the extent of energy absorption is the wavelength of the light used and the optical properties of the tissue. Others include pigmentation, water content, mineral content, heat capacity and latent heat of transformation. Lasers tissue interactions include the physiologic and mechanical processes of heat conduction and dissipation, the degree of tissue inflammation and vascularity and the availability of progenitor cells to participate in the healing process. The present article is a literature review designed to assess the rationality of using lasers in periodontal therapy.

Kallikrein–kinin system in inflammatory bowel diseases: Intestinal involvement and correlation with the degree of tissue inflammation

Background. Tissue kallikrein and its natural inhibitor, kallistatin, play opposite roles in the generation of bradykinin, a potent mediator of inflammation. Observations on experimental models and humans with ulcerative colitis suggest a pathogenetic role of the kallikrein–kinin system in inflammatory bowel diseases. Aim. To evaluate tissue kallikrein and kallistatin in intestinal tissue samples from Crohn's disease and ulcerative colitis patients with different degrees of disease involvement. Patients and methods. Full-thickness surgical intestinal samples were obtained from 144 subjects (38 normal controls, 32 inflammatory controls, 38 Crohn's disease, 36 ulcerative colitis) and tested for kallikrein and kallistatin by immunoperoxidase techniques. Results. Compared with controls, kallikrein immunoreactivity was significantly weaker in goblet cells ( p = 0.0001) and significantly stronger in interstitium ( p = 0.0001) of the Crohn's disease and ulcerative colitis samples. Kallistatin colocalised with kallikrein, with almost no reactivity in goblet cells but strong reactivity in interstitium of inflammatory bowel disease patients ( p = 0.0001 versus controls). The kallikrein and kallistatin depletion of goblet cells and the increased interstitial kallikrein and kallistatin reactivity correlated with the degree of tissue inflammation ( p = 0.0001). Disease-free samples had normal kallikrein and kallistatin patterns. Conclusions. Kallikrein–kinin system is actively involved in inflammatory bowel disease as a result of the release of kallikrein in the intestinal extracellular space; this involvement correlates with the degree of tissue inflammation. The normal pattern observed in the disease-free samples seems to rule out a genetic defect of kallikrein and kallistatin in inflammatory bowel diseases.

Protective effect of Jiechangning decoction in treating experimental ulcerative colitis in guinea pigs.

To study the therapeutic effects and mechanism of Jiechangning (JCN) decoction on carrageenan induced experimental ulcerative colitis (UC). After sensitizing guinea pigs with carrageenan, we established UC animal models by free drinking water containing 2% acid degraded carrageenan (ADC). JCN decoction was orally administered once a day for 2 weeks after carrageenan treatment. Salicylazosulfapyridine (SASP) and normal saline were given to the other two groups as control. The levels of colon lipid peroxide (LPO), acid phosphatase (ACP) activity and tumor necrosis factor-alpha (TNF-alpha) were measured; colitis activity score (CAS) was carried out for assessment of the degree of tissue inflammation and injury; the colonic pathological changes were examined simultaneously with hematoxylin and eosin (HE) and toluidine blue staining used to evaluate the therapeutic effects of JCN decoction and SASP. Experimental colitis models resembling human UC were successfully induced. The levels of tissue LPO, ACP activity and the content of tissue TNF-alpha were markedly increased in the model group as compared with the normal control group (P < 0.01) and were positively correlated with CAS. JCN decoction could reverse these changes like SASP. HE staining showed that JCN decoction and SASP could reduce CAS and the degree of tissue injury, toluidine blue staining revealed that mucosa and submucosa red metachromasia pellets in JCN group and SASP group were markedly fewer than those in the model group. JCN decoction is effective in treating experimental UC, which provides theoretical basis for its clinical application.

Leukotriene antagonism reduces the generation of endothelin-1 and interferon-γ and inhibits eosinophilic airway inflammation

The cysteinyl leukotrienes (cysLTs) and the peptide hormone endothelin (ET)-1 are potent bronchoconstrictor substances, and these mediators are also claimed to be implicated in the development of eosinophilic airway inflammation. In the present study, we have investigated the effect of the cysLT 1 receptor antagonist montelukast on the development of an eosinophilic airway inflammation 24 h after intratracheal Sephadex (SDX) provocation in rats. Furthermore, the effect of montelukast treatment on the generation of ET-1 and other pro-inflammatory mediators has been studied. The inflammatory response was significantly reduced in the animals receiving SDX + montelukast compared to animals receiving solely SDX, as evaluated by a decrease in bronchoalveolar lavage fluid total cell count (10.3±1.2 vs. 18.5±1.8×10 4 ml −1, P<0.001), number of eosinophils (299.7±43.8 vs. 577.6±46.6×10 2 ml −1, P<0.001), and lymphocytes (116.8±20 vs. 222.0±34.8× 10 2 ml −1, P<0.05), as well as the degree of tissue inflammation ( P<0.05). Montelukast also inhibited the increase in the concentration of the pro-inflammatory mediators ET-1 (28.5±7.5 vs. 40.9±7.3×pg ml −1, P<0.05) and interferon (IFN)-γ (4.3±2.2 vs. 15.6±8.7×pg ml −1, P<0.05), but not tumor necrosis factor-γ or interleukin-8. In summary, treatment with the cysLT 1 receptor antagonist montelukast reduced the inflammatory response during development of an eosinophilic airway inflammation, possibly by inhibiting the release of pro-inflammatory mediators like ET-1 and IFN-γ.

NK-1 receptor gene expression is related to pain in chronic pancreatitis

Recent theories of pathogenesis of pain in chronic pancreatitis (CP) are neuroimmune interactions of intrapancreatic nerves and inflammatory cells and increase in levels of pain neurotransmitters such as substance P (SP). This study analyzed the expression and localization of neurokinin 1 receptor (NK-1R), which binds SP, and its association with pain and inflammation in CP. Pancreatic tissues from 31 patients (22 males, nine females; mean age 45.9±9.4 years) with CP were evaluated. Nine normal pancreases (five males, four females; mean age 42.9±9.5 years) served as controls. Quantitative PCR was used to determine the NK-1R mRNA expression levels and in situ hybridization and immunohistochemistry were used to localize expression sites of NK-1R mRNA and protein, respectively. We also analyzed whether an association exists between NK-1R mRNA expression and pain and inflammation. In CP samples, in situ hybridization and immunohistochemistry localized NK-1R mRNA expression and protein mainly in the nerves, ganglia, blood vessels, inflammatory cells and occasionally in fibroblasts. In patients with mild to moderate and strong intensity of pain, NK-1R mRNA levels were increased 14- and 30-fold over controls, respectively. There was a significant relationship between NK-1R mRNA levels and intensity of pain ( r=0.46, P=0.03), NK-1R mRNA and the frequency of pain ( r=0.51, P=0.04), and NK-1 mRNA and duration of pain ( r=0.46, P=0.01) in CP patients, but not with the degree of tissue inflammation. NK-1R signaling may be involved in the pain syndrome of CP. The expression of NK-1R in inflammatory cells and blood vessels also points to an interaction of immunoreactive substance P nerves, inflammatory cells and blood vessels, and further supports the existence of a neuroimmune interaction that probably influences the pain syndrome and chronic inflammatory changes so characteristic of CP.

Middle ear pathologic changes associated with chronic anaerobic sinusitis in rabbits.

To study the histopathologic changes in association with the inflammatory/immune response present in the middle ears of a rabbit model of unilateral chronic anaerobic sinusitis. New Zealand white rabbits, two at each experimental time point. Normal rabbits and sham-operated animals served as controls. Left maxillary sinusitis was induced by inoculating Bacteroides fragilis surgically after closure of the ostium. Cultures, lavages, and mucosa were harvested from bilateral middle ear and sinus cavities at 1, 2, 3, and 4 weeks following inoculation. Parameters analyzed include tissue for histopathologic study, immunoglobulin G antibody (IgG Ab) against B fragilis, and lactate dehydrogenase (LDH) levels in lavage samples, interferon gamma (IFN gamma) messenger RNA (mRNA) expression in mucosal tissue, and bacterial culture. Despite closure of the ostium of the left sinus, mild to moderate dissemination of B fragilis into the right sinus and left and right ears were observed in some but not all rabbits (2/8, 5/7, and 2/8, respectively). Histopathologic changes in the right sinus and middle ears were much less severe in contrast to the severe inflammatory changes in the left sinus. An immune response against B fragilis appeared to occur in the sinuses and ears bilaterally independent of bacterial dissemination, as evidenced by a rise of IgG Ab in lavage fluid and detection of IFNg mRNA. Neither control nor sham-operated animals had detectable levels of IFNg mRNA or IgG Ab. In B fragilis-inoculated rabbits, the magnitude of IgG Ab responses was equivalent in the right and left ear, independent of B fragilis dissemination; IgG Ab levels in the middle ear positively correlated to each other (P < .01) and to the levels in the sinuses (P < .01 and P < .01). LDH levels were closely associated with bacterial growth and degree of tissue inflammation. This reproducible model of chronic sinusitis provides an opportunity to study the middle ear infection and inflammatory/immune responses occurring with sinusitis. Our results indicate bilateral middle ear mucosal immune responses to an elicited sinus infection, independent of B fragilis dissemination.

PREGNANCY LOSS IN AUTOIMMUNE DISEASES

Systemic autoimmune diseases are chronic inflammatory disorders that vary in organ involvement and degree of tissue inflammation. The marked female predominance increases the importance of understanding pregnancy effects on these disorders. Risk of disease exacerbation and fetal loss is variable, depending on the specific disorder, the current activity of disease, the time of disease onset, and the presence of particular autoantibodies. Prior joint or organ system damage may impact pregnancy course and delivery.

Pathophysiology and principles of pain management in rheumatic diseases.

Pain is a major presenting symptom in patients with rheumatic diseases. It is difficult, however, to define pain precisely because there are both objective and subjective components to the experience of pain. Thus, patients with the same degree of tissue inflammation may experience different levels of pain. The variation in individual pain experience often presents us with a diagnostic and therapeutic dilemma. Pain management, therefore, must be based on a solid understanding of the pathophysiology of pain and on a careful review of the risks, benefits, cost, and efficacy of available treatments.

Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis.

Interleukin 1 (IL-1) may be a key mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). In rabbits with immune complex-induced colitis, IL-1 alpha and beta mRNA levels were detectable at 4 h, peaked at 12 but were absent at 96 h after the induction of colitis. Colonic IL-1 tissue levels were measured by specific radioimmunoassays. IL-1 alpha was significantly elevated at 4 h (9.4 +/- 1.5 ng/g colon), progressively increased at 48 h (31 +/- 5.8 ng/g) and then decreased by 96 h (11.5 +/- 3.4 ng/g). IL-1 beta levels were 2.0 +/- 0.5 ng/g colon at 4 h, 5.0 +/- 1.6 ng/g at 48 h and undetectable by 96 h. By comparison, colonic levels of PGE2 and LTB4 were unchanged during the first 12 h and did not become elevated until 24 h. IL-1 alpha levels were highly correlated with inflammation (r = 0.885, P less than 0.0001), edema (r = 0.789, P less than 0.0001) and necrosis (r = 0.752, P less than 0.0005). Treatment with a specific IL-1 receptor antagonist (IL-1 ra) before and during the first 33 h after the administration of immune complexes markedly reduced inflammatory cell infiltration index (from 3.2 +/- 0.4 to 1.4 +/- 0.3, P less than 0.02), edema (from 2.2 +/- 0.4 to 0.6 +/- 0.3, P less than 0.01) and necrosis (from 43 +/- 10% to 6.6 +/- 3.2%, P less than 0.03) compared to vehicle-matched colitis animals. These studies demonstrate that (a) IL-1 gene expression and synthesis occur early in the course of immune complex-induced colitis; (b) are significantly elevated for 12 h before the appearance of PGE2 and LTB4; (c) tissue levels of IL-1 correlate with the degree of tissue inflammation and; (d) specific blockade of IL-1 receptors reduces the inflammatory responses associated with experimental colitis.