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A summary of the current understanding of the physiological role and mechanism of action of the prostaglandin endoperoxide synthase or cyclooxygenase (COX) with respect to its implication in various disease pathology is presented. The two COX isoforms, COX-1 and COX-2 are studied using the nonsteroidal anti-inflammatory drugs as well as COX-2 selective inhibitors.

Background: Although the contractile, migratory, and proliferative responses of subepithelial myofibroblasts to injury have been postulated to be important events in intestinal wound healing, contractile force generation and migration by [...]

The slow rolling motion of leukocytes along the walls of blood vessels mediated by specific receptor-ligand adhesion is important in inflammation and occurs in postcapillary venules over a wide range of wall shear stresses and vessel diameters. The ability of hydrodynamic collisions between cells to induce capture of free-stream leukocytes to a selectin-bearing surface under shear flow was studied experimentally by using a cell-free assay. It was found that carbohydrate-coated spherical beads, representing model leukocytes, tend to attach to the adhesive wall 4-5 cell diameters up- or downstream of a slowly rolling or stationary adhesive bead. A key feature of such 'hydrodynamic recruitment' is that only glancing, indirect collisions occurring close to the plane will result in downstream attachment. A direct numerical simulation of cell capture and rolling that includes multiparticle hydrodynamic interactions is shown to reproduce the observed behavior accurately. The theory predicts that hydrodynamic recruitment will occur in the absence of buoyancy effects and over a range of shear rates, suggesting that the mechanism may be important in vivo. This theory is supported by measurements of leukocyte capture in vivo using the hamster cheek pouch model.

Byline: S. Gando (1), J. Nishihira (2), S. Kobayashi (1), Y. Morimoto (1), S. Nanzaki (1), O. Kemmotsu (1) Keywords: Macrophage migration inhibitory factor (MIF) Systemic inflammatory response syndrome (SIRS) Multiple organ dysfunction syndrome (MODS) Tumor necrosis factor- (TNF-) Cortisol Abstract: Objective: To determine the relations between macrophage migration inhibitory factor (MIF), tumor necrosis factor-[alpha] (TNF-[alpha]), interferon-I3 (IFN-I3), and cortisol in patients with systemic inflammatory response syndrome (SIRS) and to determine whether their levels correlate with patient survival. Design: Prospective, observational, cohort study. Setting: General intensive care unit in a university hospital. Patients and participants: The study included 17 consecutive patients who met the criteria for SIRS the patients were classified into subgroups, survivors (n = 8) and nonsurvivors (n = 9) eight healthy volunteers served as control subjects. Interventions: None. Measurements and results: Serum MIF, TNF-[alpha], IFN-I3, and cortisol levels were measured serially when the patients were first identified as having SIRS (day 0), and on days 1--4. Except for the high tendency of acute respiratory distress syndrome in nonsurvivors (44%) compared to survivors (13%), there were no differences in the clinical backgrounds of the patients between the two groups. All patients had multiple organ dysfunction syndrome. The values of MIF and TNF-[alpha] in the nonsurvivors were significantly more elevated than those cytokines measured in the survivors and control subjects. Peak MIF levels significantly correlated with peak TNF-[alpha] levels (r .sup.2 = 0.448, P = 0.002), but did not correlate with peak levels of cortisol and IFN-I3. Although the levels of IFN-I3 and cortisol showed a marked increase compared to those of the control subjects, we could not find differences in these variables between the survivors and the nonsurvivors. Conclusions: High MIF and TNF-[alpha] levels are closely linked with poor outcome in patients with SIRS. MIF and TNF-[alpha] may act together and have pathogenic roles in SIRS. Author Affiliation: (1) Department of Anesthesiology and Critical Care Medicine, Hokkaido University School of Medicine, N15, W7, Kita-ku, Sapporo 060, Japan (2) Central Research Institute, Hokkaido University School of Medicine, N15, W7, Kita-ku, Sapporo, Japan Article History: Received Date: 03/03/2000 Accepted Date: 14/11/2000 Article note: Final revision received: 16 October 2000 Electronic Publication

Results demonstrate that heparin antagonists Polybrene and protamine strongly inhibit both human lung tryptase and recombinant mouse tryptase. Data indicate that while protamine inhibition is competitive that of Polybrene is noncompetitive, which is accompanied by monomer formation and loss of the enzyme activity.

Research reveals that caspase activation in endothelial cells inhibits nuclear factor kB-dependent activation suggesting a relationship between proapoptotic and anti-inflammatory pathways. Data demonstrate alpha-tocopheryl succinate induced effects of endothelial cell apoptosis and p65 cleavage are related and involvement of caspases in p65 cleavage.

The host response to viral infections is reflected in the production of cytokines and chemokines mediated by the interaction of cellular receptors and viral glycoproteins. Data reveal that viral RNA and viral proteins interfere with signal transduction pathways in the host leading to viral replication and expression of proinflammatory proteins.

The inflammatory response of endothelial cells is mediated by CD36 and activated leukocytes release the myeloid-related proteins S100A8 and S100A9 at inflammatory sites. Interaction between CD36 and the myeloid proteins is involved in inflammation process in that they mediate recruitment and activation of cellular effectors for host response.

Researchers report that some HIV patients who have a good response to AIDS drugs may still have increased levels of inflammatory substances in their cerebrospinal fluid. This could indicate that HIV continues to reproduce in the brain but cannot be detected by RNA tests.

Research has shown that coronary artery disease may have an inflammatory component. Inflammatory proteins are produced by the liver, immune cells, and blood vessels.

Lung anaphylaxis, an immediate allergic reaction characterized by upper and/or lower airway obstruction and inflammation, shares some important features with asthma, such as bronchoconstriction and airway hyperresponsiveness (AHR). Tachykinins play a role in both antigen-induced bronchoconstriction and AHR. Although it is known that cysteinyl leukotrienes contract bronchial smooth muscle and increase tachykinin release from sensory nerves, little information exists on the interactions between tachykinins and cyclooxygenase metabolites in the airways. Indirect evidence indicates that tachykinins might contribute to antigen-induced bronchoconstriction by stimulating cyclooxygenation of arachidonic acid. Investigation of the interactions between tachykinins and eicosanoids can provide new insights into the pathophysiology of asthma and suggest new sites for its pharmacological modulation.

Following an injury, the body recruits a mechanism to delimit and repair tissue damage; this phenomenon is known as inflammation. Among the several different pathways that are activated during this process, which is necessary for survival, activation of the coagulation pathway is a key feature. In fact, clinical changes in blood fluidity have been closely related to ongoing inflammation. Recent evidence suggests that serine protease receptors might play a major role in the host defence mechanism at the interface between coagulation and inflammation.

Research illustrates the synthesis of a novel sialyl Lewis X (sLe(sup)x) mimetic by a convergent route employing 1-thio-1,2-O-isopropylidene precursor.

Blood levels of C-reactive protein (CRP) can be used to diagnose cardiovascular disease in women. This protein is a marker of inflammation in the body. In a study of 28,263 healthy postmenopausal women, CRP was the strongest predictor of a future heart attack or stroke. Women with the highest blood CRP levels had 4 times the risk of a heart attack or stroke. Blood levels of amyloid A, homocysteine, total cholesterol, LDL and HDL cholesterol, and apolipoprotein B-100 were also important. Elevated blood lipid levels and markers of inflammation were better predictors than blood lipid levels alone.

Cell-surface protease-activated receptors (PARs) appear to have evolved to detect extracellular enzymatically active serine proteases such as trypsin and thrombin. The predominant location of PARs on endothelia and epithelia and the discovery of enzymes such as trypsin within these tissues, together with the linkage of PARs to cytoprotective pathways, provide new information on autocrine and paracrine signalling within these critical barriers. In this article, the ways in which the distribution and function of PARs could be harnessed by pharmacologists as novel anti-inflammatory therapeutic strategies are discussed.

Relatively little is known about changes in soluble receptors and other agonists/antagonists that may regulate cytokine actions in aging humans. We have studied age-associated changes in human subjects of (a) the plasma levels of interleukin-1 soluble receptor (IL-1sII), interleukin-1 receptor antagonist (IL-1ra), tumor necrosis factor soluble receptor-II (75kDa; TNFsRII), and interleukin-6 soluble receptor (IL-6sR) and (b) the ability of their blood mononuclear cells to produce those soluble factors spontaneously and after phytohemagglutinin (PHA) stimulation. Aging subjects (50-67 years) had significantly higher plasma levels of IL-1ra, significantly lower levels of TNFsRII and IL-6sR than young subjects (25-35 years), and no significant change in the level of IL-1sRII. There was less spontaneous output of IL-1ra and TNFsRII by peripheral blood mononuclear cells (PBMC) of aging than of young subjects, but equivalent output of both factors in response to PHA stimulation. Thus, the basal (homeostatic) output of those two factors declined with age, but the potential of the PBMC to produce the factors on stimulation did not. PHA stimulation of PBMC of either age group significantly inhibited the output of IL-6sR. These differences between the young adult and aging subjects, along with reported changes in the corresponding cytokines, presumably foreshadow changes that become more marked with further aging. Therefore, immunological processes that depend on, or are modulated by, proinflammatory cytokines may differ between young and aged subjects as a consequence of the availability of regulatory soluble receptors and related agonists or antagonists. The results of this study highlight the need for further studies of the roles played by soluble receptors, and similar agonists/antagonists, in the immune responses of aged adults.

Researchers have discovered a peptide produced by monocytes in the presence of glucocorticoids that has anti-inflammatory properties. Thymosin beta4 sulfoxide inhibited neutrophil chemotaxis and limited edema in a study in mice.

Inflammation-associated tissue destruction involves proteinase inhibition by alpha2-macroglobulin (alpha2-M), a broad-spectrum proteinase inhibitor in plasma and interstitial fluid. Patients with emphysema, sepsis, rheumatoid arthritis, peridontitis and other inflammatory diseases demonstrate high levels of alpha2-M and proteinase. Since an oxidant that can inactivate alpha2-M has not been discovered, hypochlorite can be used to destroy the proteinase inhibition capability of alpha2-M.

Histamine, serotonin and leukotriene D4 radically increase the electrical field stimulation-induced smooth muscle contractions in horse airways, in addition to their direct contractile effects. To elucidate on the mechanism of their action, the effect of these mediators on both cholinergically induced tension and the release of acetylcholine from cholinergic nerves was investigated in trachealis strips. Results showed that inflammatory mediators can enhance endogenous cholinergic responses of horse airways via both prejunctional and postjunctional mechanisms.

Inflammatory pain manifests as spontaneous pain and pain hypersensitivity. Spontaneous pain reflects direct activation of specific receptors on nociceptor terminals by inflammatory mediators. Pain hypersensitivity is the consequence of early posttranslational changes, both in the peripheral terminals of the nociceptor and in dorsal horn neurons, as well as later transcription-dependent changes in effector genes, again in primary sensory and dorsal horn neurons. This inflammatory neuroplasticity is the consequence of a combination of activity-dependent changes in the neurons and specific signal molecules initiating particular signal-transduction pathways. These pathways phosphorylate membrane proteins, changing their function, and activate transcription factors, altering gene expression. Two distinct aspects of sensory neuron function are changed as a result of these processes, basal sensitivity, or the capacity of peripheral stimuli to evoke pain, and stimulus-evoked hypersensitivity, the capacity of certain inputs to generate prolonged alterations in the sensitivity of the system. Posttranslational changes largely alter basal sensitivity. Transcriptional changes both potentiate the system and alter neuronal phenotype. Potentiation occurs as a result of the up-regulation in the dorsal root ganglion of centrally acting neuromodulators and simultaneously in the dorsal horn of their receptors. This means that the response to subsequent inputs is augmented, particularly those that induce stimulus-induced hypersensitivity. Alterations in phenotype includes the acquisition by A fibers of neurochemical features typical of C fibers, enabling these fibers to induce stimulus-evoked hypersensitivity, something only C fiber inputs normally can do. Elucidation of the molecular mechanisms responsible provides new opportunities for therapeutic approaches to managing inflammatory pain.

Several mechanisms have been identified that may underlie inflammation-induced sensitization of high-threshold primary afferent neurons, including the modulation of voltage- and [Ca.sup.2+]-dependent ion channels and ion channels responsible for the production of generator potentials. One such mechanism that has recently received a lot of attention is the modulation of a tetrodotoxin (TTX)-resistant voltage-gated [Na.sup.+] current. Evidence supporting a role for TTX-resistant [Na.sup.+] currents in the sensitization of primary afferent neurons and inflammatory hyperalgesia is reviewed. Such evidence is derived from studies on the distribution of TTX-resistant [Na.sup.+] currents among primary afferent neurons and other tissues of the body that suggest that these currents are expressed only in a subpopulation of primary afferent neurons that are likely to be involved in nociception. Data from studies on the biophysical properties of these currents suggest that they are ideally suited to mediate the repetitive discharge associated with prolonged membrane depolarizations. Data from studies on the effects of inflammatory mediators and antinociceptive agents on TTX-resistant [Na.sup.+] currents suggest that modulation of these currents is an underlying mechanism of primary afferent neuron sensitization. In addition, the second-messenger pathways underlying inflammatory mediator-induced modulation of these currents appear to underlie inflammatory mediator-induced hyperalgesia. Finally, recent antisense studies have also yielded data supporting a role for TTX-resistant [Na.sup.+] currents in inflammatory hyperalgesia. Although data from these studies are compelling, data presented at the Neurobiology of Pain colloquium raised a number of interesting questions regarding the role of TTX-resistant [Na.sup.+] currents in inflammatory hyperalgesia; implications of three of these questions are discussed.

A study was conducted to analyze whether extracellular ATP could promote P(sub 2Z)/P2X(sub 7) receptor-dependent apoptosis of dendritic cells. The immortalized dendritic cell line was obtained from Balb/c mouse spleen. Experimental results indicated that dendritic cells express a functional P(sub 2Z)/P2X(sub 7) receptor capable of starting apoptosis after its engagement by ATP(sub 0).

The response of C3H/HeBFeJ mice exposed to sterile corn dust extract (CDE) was compared to the response shown after inhalation of liposaccharide (LPS). Results showed that after CDE and LPS exposure, the mice exhibited increases in neutrophil concentration one hour after inhalation, an effect that persisted for 48 hours. Concentrations of tumor necrosis factor-alpha, interleukin-1(alpha) and macrophage inflammatory protein were also observed to increase. The findings suggest that inhalation of corn dust or endotoxins is primarily mediated by inflammatory cells and is largely self-limited.

Research was conducted to examine the effects of mediators such as histamine, serotonin and leukotrienes and the effects of activated neutrophils on the cholinergic responses in equine small airways (SA). Results indicate that endogenous cholinergic response in equine SA are subject to strong facilitation by inflammatory mediators, that histamine, LTD4 and serotonin contribute to increased cholinergic airway tone and that activated neutrophils have no effect on cholinergic responses in SA.

The kinins, particularly bradykinin (BK), are important mediators involved in both the initiation and progression of an inflammatory response. The pro-inflammatory effects of kinins are mediated by at least two receptors: the [B.sub.2] subtype is expressed constitutively and the [B.sub.1] receptor is induced following tissue inflammation and damage. The endogenous ligand for the [B.sub.1] receptor is des-[arg.sup.9]BK, a cleavage product of the activity of carboxypeptidases on BK. Activation of [B.sub.1] receptors produces a range of pro-inflammatory effects including oedema, pain and promotion of blood-borne leukocyte trafficking. In this article Amrita Ahluwalia and Mauro Perretti briefly describe the biology of BK and its receptors, and discuss the possible development of [B.sub.1] receptor antagonists as novel anti-inflammatory agents.

Acute-phase proteins are proteins whose synthesis is increased or decreased during inflammation, infections, trauma, burns, surgery and cancer. Some acute-phase proteins stimulate inflammation and others have anti-inflammatory actions. Acute-phase proteins include the complement system, the blood coagulation and thrombolytic system, antiproteases, transport proteins and other general proteins such as C-reactive protein and serum amyloid A. Most acute-phase proteins are regulated by immune system proteins such as the interleukins and interferons and tumor necrosis factor. Measuring blood levels of C-reactive protein and the erythrocyte sedimentation rate are the most common means of detecting an acute-phase reaction.

A grasp of the molecular kinetic parameters for adhesion molecule interactions is necessary to gauging the relative contribution of various receptor pairs to the rolling of leukocytes in the vasculature. A study was conducted to investigate the affinity of soluble P-selectin for the soluble P-selectin glycoprotein ligand-1 in a simple, chemically defined system where two components could be observed in the solution phase.

The mechanisms that exacerbate inflammatory response to ischemia-reperfusion in diabetes were investigated. Specifically, the role of lipid mediators and adhesion molecule expression in enhanced ischemia-reperfusion-induced inflammatory response was examined. Experimental results showed that diabetes significantly enhances the inflammatory response to ischemia-reperfusion and that both the platelet-activating factor and leukotrienes play an essential role in the pathogenesis of this inflammatory response.

An inflammatory process in the lung may be the cause of bronchopulmonary dysplasia (BPD). BPD occurs when premature infants are given supplemental oxygen to treated respiratory distress syndrome. However, the oxygen damages the immature lungs, leading to BPD. Researchers analyzed cord blood samples from 25 newborn premature infants for proteins in the body that allow white blood cells to reach areas of inflammation. The levels of the proteins E-selectin and ICAM-1 were higher in infants who subsequently developed BPD., Objective. To test the hypothesis that in infants born at [is less than or equal to] 29 weeks' gestation soluble adhesion molecule concentrations would be higher in the first week of life in infants that subsequently develop bronchopulmonary dysplasia than in infants that do not. Design and Methods. In cord blood and on days of life 1, 3, and 7, we measured serum concentrations of soluble P-Selectin, E-Selectin, and intercellular adhesion molecule-1 in samples obtained from infants [is less than or equal to]29 weeks' gestational age. At 1 month of age we assessed the infants' clinical courses to determine whether the infants met the criteria for the diagnosis of bronchopulmonary dysplasia (BPD) and evaluated the infants' radiographic studies to stage the level of BPD. On discharge, the duration of oxygen therapy, the requirement for home oxygen therapy, and length of hospital stay were determined. Results. Concentrations of soluble P-Selectin were greatest in cord blood samples obtained from all infants and were markedly reduced on day of life 1, regardless of the subsequent development of BPD. In serum samples obtained from cord blood and on days of life 1 and 3, soluble E-Selectin levels were higher in infants that developed BPD than in infants that did not develop BPD. In addition, the highest concentrations of soluble E-Selectin in serum samples from cord blood and on day of life 1 were associated with the development of stage 3 or 4 BPD. Soluble intercellular adhesion molecule-1 concentrations were higher on days of life 3 and 7 in the infants that went on to develop BPD than in those that did not. Conclusions. Because neutrophil attachment to endothelial cell adhesion molecules is a key event in the initiation of an inflammatory response, the association of higher early concentrations of soluble E-Selectin with the development of BPD suggests that E-Selectin may play a key role in the pathogenesis of lung inflammation and the development of BPD. This association also suggests that inflammatory events or effects leading to inflammatory responses occurring in the prenatal and/or very early perinatal periods contribute significantly to the pathogenesis of BPD. Pediatrics 1998;102:927-932; bronchopulmonary dysplasia, infant, newborn, cell adhesion molecules, lung diseases., ABBREVIATIONS. BPD, bronchopulmonary dysplasia; ICAM-1, intercellular adhesion molecule-1; sP-Selectin, soluble P-Selectin; sE-Selectin, soluble E-Selectin; sICAM-1, soluble ICAM-1. Bronchopulmonary dysplasia (BPD) remains a major cause of morbidity for the prematurely born [...]

The mutation of the interfacial valine of human secreted phospholipase A2 (sPLA2) to a tryptophan was found to demonstrate the ability of this amphiphilic indole residue. The residue substantially improves the hydrolysis of zwitterionic interfaces found in the form of small unilamellar vesicles of phosphatidylcholine or cell membranes. Findings are in good agreement with the function of interfacial tryptophans of venom enzymes in permitting the penetration and hydrolysis of such condensed bilayers.

The transcription factor NF-varKappaBeta is involved in coordinating the activation of many genes in response to pathogens and pro-inflammatory cytokines. IKK-alpha has been independently discovered as a NF-varKappaBeta-inducing kinase (NIK)-associated protein in a yeast, but it is not known if NIK is part of the IKK complex. Interleukin-1-inducible IKK complexes containing NIK, IKK-alpha, IKK-beta, IvarKappaB-alpha, NF-varKappaB/RelA and a protein of Mr 150K, was isolated. It is shown that IKAP is a scaffold protein and a regulator for kinases involved in pro-inflammatory cytokine signalling.

The molecular mechanisms regulating expression in the BEAS-2B bronchial epithelial cell line of the granulocyte macrophage-colony stimulating factor (GM-CSF) in airway epithelial cells were described. It was observed that de novo protein synthesis was not essential in the induction of GM-CSF by interleukin 1beta (IL-1beta). Transcriptional mechanisms were identified as the major promoters of IL-1beta activation and glucocorticoid inhibition of GM-CSF.

Implanted biomaterials trigger acute and chronic inflammatory responses. The mechanisms involved in such acute inflammatory responses can be arbitrarily divided into phagocyte transmigration, chemotaxis, and adhesion to implant surfaces. We earlier observed that two chemokines - macrophage inflammatory protein 1[Alpha]/monocyte chemoattractant protein 1 - and the phagocyte integrin Mac-1 (CD11b/CD18)/surface fibrinogen interaction are, respectively, required for phagocyte chemotaxis and adherence to biomaterial surfaces. However, it is still not clear how the initial transmigration of phagocytes through the endothelial barrier into the area of the implant is triggered. Because implanted biomaterials elicit histaminic responses in the surrounding tissue, and histamine release is known to promote rapid diapedesis of inflammatory cells, we evaluated the possible role of histamine and mast cells in the recruitment of phagocytes to biomaterial implants. Using i.p. and s.c. implantation of polyethylene terephthalate disks in mice we find: (i) Extensive degranulation of mast cells, accompanied by histamine release, occurs adjacent to short-term i.p. implants. (ii) Simultaneous administration of H1 and H2 histamine receptor antagonists (pyrilamine and famotidine, respectively) greatly diminishes recruitment and adhesion of both neutrophils (< 20% of control) and monocytes/macrophages (< 30% of control) to implants. (iii) Congenitally mast cell-deficient mice also exhibit markedly reduced accumulation of phagocytes on both i.p. and s.c implants. (iv) Finally, mast cell reconstitution of mast cell-deficient mice restores 'normal' inflammatory responses to biomaterial implants. We conclude that mast cells and their granular products, especially histamine, are important in recruitment of inflammatory cells to biomaterial implants. Improved knowledge of such responses may permit purposeful modulation of both acute and chronic inflammation affecting implanted biomaterials.

Interleukin-1beta induces the biosynthesis of nitric oxide and prostaglandin E2 in mesangial cell cultures from rat kidneys. This induction is enhanced in the presence of insulin and insulin-like growth factor-I (IGF-I) by inducing the translation of inducible nitric oxide and cyclooxygenase. Both IGF-I and insulin also enhances the phosphorylation of the mitogen-activated protein kinase. The implications of these findings on the inflammatory processes taking place in the kidneys are discussed.

Immunohistochemical techniques were used to demonstrate the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) in the liver sinusoids and the mesenteric vessels of control and endotoxin-treated mice to investigate its role in hepatic and peritoneal inflammation during endotoxemia. Results reveal that PECAM-1 is not involved in hepatic inflammatory reactions following endotoxemia but it mediates neutrophil transmigration during peritoneal inflammation.

Research indicates that circulating S-nitrosothiols are not responsible for the peroxynitrite-mediated vasodilation and hypotension seen in anaethetized rats. Experiments using anesthetized rats show that the presence of L-penicillamine has no impact on the hemodynamic effects of peroxynitrite. Further research is required to establish how peronitrite brings about vasodilatation.

The inhibition of selectin-ligand binding is necessary to disrupt the over recruitment of lymphocytes from the vasculature to the site of injury because over recruitment of lymphocytes results to chronic inflammatory diseases. Despite the importance of selectins in inflammation for they function as cell-surface receptor, selectin antagonists are necessary to avoid abnormal function of the receptor. These antagonists may help in regulating abnormal adhesion and recruitment of lymphocytes.

Chemokines are proteins produced by the immune system that can attract immune cells to the site of an injury or inflammation. There are over 40 known chemokines and they attract white blood cells, including T cells, neutrophils and natural killer cells. However, chemokine receptors occur on other tissues, including neurons and epithelial cells but their role in these tissues is unclear. Their most important function is to assist the white blood cell in moving from the blood into the tissues, a process called extravasation. Chemokines have been found in many chronic diseases, so blocking their action may have important therapeutic implications.

The role of different prostaglandin analogs on interstitial fluid extravasation during the inflammatory response is investigated by evaluating their effects on collagen gel compaction in in vitro systems and subdermal inflammation in anesthetized rats. Results indicate that prostaglandins have novel effects on the extracellular matrix that regulate the interstitial fluid pressure during inflammation.