IL-36 family cytokines in protective versus destructive inflammation

2020 ◽  
Vol 75 ◽  
pp. 109773 ◽  
Author(s):  
Yingying Han ◽  
Arnaud Huard ◽  
Javier Mora ◽  
Priscila da Silva ◽  
Bernhard Brüne ◽  
...  
2021 ◽  
pp. 019262332097839
Author(s):  
Meg Ferrell Ramos ◽  
Jacqueline Brassard ◽  
Sharmila Masli

Clear vision is dependent on features that protect the anatomical integrity of the eye (cornea and sclera) and those that contribute to internal ocular homeostasis by conferring hemangiogenic (avascular tissues and antiangiogenic factors), lymphangiogenic (lack of draining lymphatics), and immunologic (tight junctions that form blood–ocular barriers, immunosuppressive cells, and modulators) privileges. The later examples are necessary components that enable the eye to maintain an immunosuppressive environment that responds to foreign invaders in a deviated manner, minimizing destructive inflammation that would impair vision. These conditions allowed for the observations made by Medawar, in 1948, of delayed rejection of allogenic tissue grafts in the anterior chamber of mouse eye and permit the sequestration of foreign invaders (eg, Toxoplasma gondii) within the retina of healthy individuals. Yet successful development of intraocular drugs (biologics and delivery devices) has been stymied by adverse ocular pathology, much of which is driven by immune pathways. The eye can be intolerant of foreign protein irrespective of delivery route, and endogenous ocular cells have remarkable plasticity when recruited to preserve visual function. This article provides a review of current understanding of ocular immunology and the potential role of immune mechanisms in pathology observed with intraocular drug delivery.


2019 ◽  
Vol 116 (20) ◽  
pp. 9989-9998 ◽  
Author(s):  
Yoko Okunuki ◽  
Ryo Mukai ◽  
Takeshi Nakao ◽  
Steven J. Tabor ◽  
Oleg Butovsky ◽  
...  

Autoimmune uveitis is a sight-threatening ocular inflammatory condition in which the retina and uveal tissues become a target of autoreactive immune cells. While microglia have been studied extensively in autoimmune uveitis, their exact function remains uncertain. The objective of the current study was to determine whether resident microglia are necessary and sufficient to initiate and amplify retinal inflammation in autoimmune uveitis. In this study, we clearly demonstrate that microglia are essential for initiating infiltration of immune cells utilizing a murine model of experimental autoimmune uveoretinitis (EAU) and the recently identified microglia-specific marker P2ry12. Initiating disease is the primary function of microglia in EAU, since eliminating microglia during the later stages of EAU had little effect, indicating that the function of circulating leukocytes is to amplify and sustain destructive inflammation once microglia have triggered disease. In the absence of microglia, uveitis does not develop, since leukocytes cannot gain entry through the blood-retinal barrier, illustrating that microglia play a critical role in regulating infiltration of inflammatory cells into the retina.


2014 ◽  
Vol 99 (5) ◽  
pp. 595-599 ◽  
Author(s):  
Fatih Taskesen ◽  
Zulfu Arikanoglu ◽  
Omer Uslukaya ◽  
Abdullah Oguz ◽  
Ibrahim Aliosmanoglu ◽  
...  

Abstract Xanthogranulomatous cholecystitis is a rare variant of chronic cholecystitis characterized by severe proliferative fibrosis and accumulation of lipid-laden macrophages in regions of destructive inflammation. Xanthogranulomatous cholecystitis clinically and radiologically mimics early-stage gallbladder cancer, with wall thickening on computed tomography. The study included 14 xanthogranulomatous cholecystitis patients that were identified following retrospective analysis of the records of 1248 patients that underwent cholecystectomy between 2005 and 2011. Mean age of the 5 male and 9 female patients was 56.7 years. All 14 patients had gallbladder stones; 10 had a history of acute cholecystitis, 1 had cholangitis, and 2 presented with obstructive jaundice. A right-upper quadrant mass was palpable in 2 patients. All patients underwent cholecystectomy. Open surgery was planned and performed in 6 of the 14 patients, and laparoscopic cholecystectomy was planned in 8 patients, but was converted to open surgery in 1 case. In total, 1 patient developed wound infection, 1 patient had postoperative pneumonia, and 1 patient developed intraabdominal hematoma. None of the patients in the series died. Xanthogranulomatous cholecystitis is difficult to diagnose, both preoperatively and intraoperatively, and definitive diagnosis depends exclusively on pathological examination. Xanthogranulomatous cholecystitis should be a consideration in all difficult cholecystectomy cases.


2012 ◽  
Vol 209 (10) ◽  
pp. 1901-1901 ◽  
Author(s):  
Monica Guma ◽  
Dariusz Stepniak ◽  
Helena Shaked ◽  
Martina E. Spehlmann ◽  
Steve Shenouda ◽  
...  

1999 ◽  
Vol 67 (3) ◽  
pp. 1471-1480 ◽  
Author(s):  
P. J. Sansonetti ◽  
J. Arondel ◽  
M. Huerre ◽  
A. Harada ◽  
K. Matsushima

ABSTRACT In shigellosis, the network of cellular interactions mediated by a balance of pro- and anti-inflammatory cytokines or chemokines is clearly tipped toward acute destructive inflammation of intestinal tissues by the bacterial invader. This work has addressed the role played by interleukin-8 (IL-8) in a rabbit model of intestinal invasion by Shigella flexneri. IL-8, which is largely produced by the epithelial cells themselves, appears to be a major mediator of the recruitment of polymorphonuclear leukocytes (PMNs) to the subepithelial area and transmigration of these cells through the epithelial lining. Neutralization of IL-8 function by monoclonal antibody WS-4 caused a decrease in the amount of PMNs streaming through the lamina propria and the epithelium, thus significantly attenuating the severity of epithelial lesions in areas of bacterial invasion. These findings are in agreement with our previous work (31). In contrast to the PMNs, the bacteria displayed increased transepithelial translocation, as well as overgrowth in the lamina propria and increased passage into the mesenteric blood. By mediating eradication of bacteria at their epithelial entry site, although at the cost of severe epithelial destruction, IL-8 therefore appears to be a key chemokine in the control of bacterial translocation.


ISRN Urology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Bülent Altunoluk ◽  
Sefa Resim ◽  
Erkan Efe ◽  
Mustafa Eren ◽  
Can Benlioglu ◽  
...  

Purpose. Fournier’s gangrene is a fulminant and destructive inflammation of the scrotum, penis, and perineum. The objective of this study was to compare 2 different approaches to wound management after aggressive surgical debridement. Methods. Data from 14 patients with Fournier’s gangrene were retrospectively collected (2005–2011). Once the patients were stabilized following surgery, they were treated with either daily antiseptic (povidone iodine) dressings (group I, n=6) or dressings with dakin’s solution (sodium hypochloride) (group II, n=8). Results. The mean age of the patients was 68.2 ± 7.8 (55–75) years in group I and 66.9 ± 10.2 (51–79) years in group II. Length of hospital stay was 13 ± 3.5 (7–16) days in group I and 8.9 ± 3.0 (4–12) days in group II (P<0.05). The number and rate of mortality was 1/6 (16.7%) in group I, and 1/8 (12.5%) in group II. Conclusions. The hospitalization time can be reduced with the use of dakin’s solution for the dressings in the treatment of FG. Also, dressings with dakin’s solution seems to have favorable effects on morbidity and mortality. Consequently dakin’s solution may alter the treatment of this disastrous disease by reducing cost, morbidity and mortality.


1883 ◽  
Vol 34 (220-223) ◽  
pp. 150-156

Professor Rosenberger, of Würzburg, has recently published the results of experiments, by which he claims to have effectually sterilised by heat, the blood and exudation fluids of the rabbit in the two forms of septichæmia, known as those of Davaine and Pasteur; and he states that these fluids so sterilised, upon injection into other animals, were found to be infective, reproducing the disease with the recurrence of the specific organisms which characterise it: he therefore regards these organisms as having no causal connexion with the affections in which they are found, but as merely secondary or epiphenomenal. That this would be the necessary deduction from the experiments mentioned, if it were proved that the fluids had been effectively sterilised, is obvious; but the account published contains no details whatever of the methods employed, nor protocol of the experiments, so that it is impossible either to discuss them or to form a judgment as to the correctness of the conclusions. They, however, involve a question so important in respect to the theory of contagium vivum—the relations of these micro-organisms to disease—that it was determined to work out the subject on the basis indicated in Professor Rosenberger’s paper, adopting such methods and precautions as appeared necessary. Guinea-pig No. 1.—0·7 cub. centim. of putrid ox-blood was injected with a Pravart’s syringe, into the peritoneal cavity of a full-grown guinea-pig, which the next morning was found recently dead, rigor not having set in: round the place of injection there was some subcutaneous exudation, with destructive inflammation of the tissues of the abdominal wall, sections of which showed numerous Bacilli and Micrococci in the layers of connective tissue between the museles. Acute peritonitis was found with a large exudation of serous fluid containing some extravasated blood-corpuscles, and deeply stained with their colouring matter. The fluid in this case was not very coagulable, differing in this respect from some others. The same day 0·5 cub. centim. of the peritoneal exudation fluid of No. 1 was injected into the subcutaneous tissue of the abdomen of guinea-pig No. 2, which, as the following day was Sunday, was not examined till Monday morning, when it was found dead, and in a much more advanced stage of decomposition than would have occurred normally in the same period. In all forms of septichæmia this rapid decomposition is invariably found. Guinea-pig No. 3 then received in similar manner 0·5 cub. centim. of the diluted subcutaneous exudation fluid of No. 2, which, likewise, was not coagulated.


2011 ◽  
Vol 208 (9) ◽  
pp. 1889-1900 ◽  
Author(s):  
Monica Guma ◽  
Dariusz Stepniak ◽  
Helena Shaked ◽  
Martina E. Spehlmann ◽  
Steve Shenouda ◽  
...  

Nuclear factor (NF)-κB, activated by IκB kinase (IKK), is a key regulator of inflammation, innate immunity, and tissue integrity. NF-κB and one of its main activators and transcriptional targets, tumor necrosis factor (TNF), are up-regulated in many inflammatory diseases that are accompanied by tissue destruction. The etiology of many inflammatory diseases is poorly understood, but often depends on genetic factors and environmental triggers that affect NF-κB and related pathways. It is unknown, however, whether persistent NF-κB activation is sufficient for driving symptomatic chronic inflammation and tissue damage. To address this question, we generated IKKβ(EE)IEC mice, which express a constitutively active form of IKKβ in intestinal epithelial cell (IECs). IKKβ(EE)IEC mice exhibit NF-κB activation in IECs and express copious amounts of inflammatory chemokines, but only small amounts of TNF. Although IKKβ(EE)IEC mice exhibit inflammatory cell infiltration in the lamina propria (LP) of their small intestine, they do not manifest tissue damage. Yet, upon challenge with relatively mild immune and microbial stimuli, IKKβ(EE)IEC mice succumb to destructive acute inflammation accompanied by enterocyte apoptosis, intestinal barrier disruption, and bacterial translocation. Inflammation is driven by massive TNF production, which requires additional activation of p38 and extracellular-signal–regulated kinase mitogen-activated protein kinases (MAPKs).


2021 ◽  
Vol 5 (2) ◽  
pp. 896-898
Author(s):  
Elena Hadzhieva ◽  
Dzhevdet Chakarov ◽  
Evgenii Moshekov ◽  
Dimitar Hadzhiev ◽  
Yordan Kalchev ◽  
...  

A supralevator anorectal abscess may lead to a rare clinical complication, such as perineal necrotizing fasciitis. A 57-year-old man was admitted on an emergency basis with evidence of a deep anorectal abscess of 5-day duration. The clinical presentation involved an unbounded purulent destructive inflammation spreading onto the adjacent areas, with the development of a septic condition. Following a short preparation, a radical surgical debridement of a subfascial purulent necrotic phlegmon of the pelvic space was performed. Since the lower part of the abdomen, retroperitoneum and scrotum were involved, 4 additional subsequent necrectomies were performed at 48-hour intervals. The aggressive radical operative treatment and the combined intensive therapy were the main contributors to the favorable outcome of the disease.


2021 ◽  
Vol 19 ◽  
Author(s):  
Jacek M. Kwiecien

: The spinal cord injury (SCI) initiates an extraordinarily protracted disease with 3 phases; acute, inflammatory and resolution that are restricted to the cavity of injury (COI) or arachnoiditis by a unique CNS reaction against the severity of destructive inflammation. While the severity of inflammation involving the white matter is fueled by a potently immunogenic activity of damaged myelin, its sequestration in the COI and its continuity with the cerebrospinal fluid of the subdural space allows for anti-inflammatory therapeutics infused subdurally to inhibit phagocytic macrophage infiltration and thus provide neuroprotection. The role of astrogliosis in containing and ultimately in eliminating severe destructive inflammation post-trauma appears obvious but is not yet sufficiently understood to use in therapeutic neuroprotective and neuroregenerative strategies. An apparent anti-inflammatory activity of reactive astrocytes is paralleled by their active role in removing excess edema fluid in blood brain barrier damaged by inflammation. Recently elucidated pathogenesis of neurotrauma including SCI, traumatic brain injury (TBI) and of stroke, calls for the following principal therapeutic steps in its treatment leading to recovery of neurologic function: (1) inhibition and elimination of destructive inflammation from the COI with accompanying reduction of vasogenic edema, (2) insertion into the COI of a functional bridge supporting the crossing of regenerating axons, (3) enabling regeneration of axons to their original synaptic targets by a temporary safe removal of myelin in targeted areas of white matter, (4) in vivo, systematic monitoring of the consecutive therapeutic steps. The focus of this paper is on the therapeutic step 1.


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