Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endothelium lining the posterior corneal surface performs physiologic pump functions essential to corneal clarity and integrity. A hallmark of keratitis, anterior ocular inflammation, and corneal allograft rejection is leukocyte adherence to the corneal endothelium (CE) forming keratitic precipitates. To elucidate mechanisms governing cornea-leukocyte interactions, cultured human CE cells and intact corneas were examined for expression of intercellular adhesion molecule-1 (ICAM-1), which binds the lymphocyte function-associated antigen-1 (LFA-1) on all leukocytes and enhances delayed-type hypersensitivity mediated by class II major histocompatibility complex antigens. Immunohistochemistry on culture CE cells using monoclonal anti-ICAM-1 antibody yield positive staining that increased after exposure to interleukin-1-beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (gamma-IFN). Standard leukocyte adherence assays demonstrated ICAM-1-mediated CE-neutrophil binding, which was specifically blocked by antibody to ICAM-1 or antibodies to LFA-1 on neutrophils. In whole human corneas, gamma-IFN increased CE and stromal keratocyte ICAM-1 immunoreactivity and enhanced CE-neutrophil adherence. As in CE cell cultures, antibody to ICAM-1 effectively blocked neutrophil binding to the CE cells of whole corneas. These results are the first to demonstrate ICAM-1 in ocular tissue. They indicate that CE cells express functional ICAM-1, which may be modulated by inflammatory cytokines, ICAM-1 provides mechanisms for keratitic precipitate formation, regulation of corneal leukocyte trafficking and the generation of immune responses that may be crucial to allograft rejection.
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PMID:Intercellular adhesion molecule-1 in human corneal endothelium. Modulation and function. 170 51

BALB/c mice infected on the scarified cornea with herpes simplex virus type 1 strain 35 [HSV-1(35)] rarely developed ocular disease even at challenge doses as high as 10(7) PFU per eye. In contrast, HSV-1(RE) consistently induced stromal keratitis at an inoculum of 2 x 10(4) PFU. The goal of this study was to determine the reason for the difference in virulence between the two HSV strains. Both HSV-1 strains replicated to similar titers in excised corneal "buttons." However, after in vivo infection of the cornea, the growth of strain 35 was evident only during the first 24 h postinfection, whereas the replication of strain RE persisted for at least 4 days. In vitro tests revealed that HSV-1(35) was greater than 10 times more sensitive to alpha/beta interferon (IFN-alpha/beta) than HSV-1(RE). Both strains induced comparable serum levels of IFN after intraperitoneal inoculation. The kinetics of HSV-1(35) clearance from the eye was markedly altered by treatment with rabbit anti-IFN-alpha/beta. Virus titers exceeding 10(4) PFU per eye could be demonstrated 4 to 5 days postinfection in mice given a single inoculation of antiserum 1 h after infection. Furthermore, anti-IFN treatment in 3-week-old mice infected with HSV-1(35) led to the development of clinically apparent corneal disease which subsequently progressed to stromal keratitis in the majority of recipients. These results indicate that the striking difference in the capacity of HSV-1(35) and HSV-1(RE) to induce corneal disease was related to the inherently greater sensitivity of strain 35 to IFN-alpha/beta produced by the host in response to infection.
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PMID:Ocular avirulence of a herpes simplex virus type 1 strain is associated with heightened sensitivity to alpha/beta interferon. 215 80

Interferons have been studied in animals and man for local and systemic viral infections that are either rare or common. Recent clinical studies in humans with purified or recombinantly derived interferons have demonstrated significant clinical response in rhinovirus common colds, herpetic keratitis, condyloma acuminata, and laryngeal papillomatosis. However, only 40 per cent of published papers with IFN have been appropriately controlled. The toxicity of these newer preparations when administered either topically or parenterally prevents their immediate licensing for general use. The toxic to therapeutic ratio for HuIFN and rIFN appears to be close to one in most clinical situations in which it has been tested. Although interferons have not proved to be the "penicillin" for viruses many thought they would become, basic in vitro work and clinical studies have contributed greatly to our understanding of host defense and immunopathology. Future studies must focus on increasing our understanding of the mechanisms of toxicity, in addition to devising controlled clinical trials with interferon alone or in combination with other antiviral agents. Thus, after 30 years of research on interferons, it would appear our work has just begun.
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PMID:Human interferon in viral diseases. 246 9

The effects of four subtypes of recombinant human alpha interferon (RIFN alpha), (A,B,D, and the hybrid A/D) were tested on six strains of herpes simplex virus (HSV). RIFN alpha -D was the most effective subtype in rabbit kidney cells, which is consistent with our previous in vivo results in the rabbit herpetic keratitis model. In human corneal cells, however, RIFN alpha -D was one of the least effective IFN subtypes tested. Conversely, RIFN alpha-A appeared to be relatively more effective in the human corneal cells than in the rabbit kidney cells, but RIFN alpha -B and RIFN alpha -A/D were the most effective interferon subtypes in human corneal cells. Different strains of HSV had different susceptibilities to the various IFN subtypes tested.
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PMID:Interferon effects on herpes simplex virus in rabbit and human cell cultures. 301 3

Forty-five patients with virologically confirmed dendritic keratitis were treated in a randomized, double-blind controlled study with a basic therapy of trifluorothymidine (TFT) eye drops. In addition they received different human recombinant interferon (rHu IFN) eye drops. The following results were obtained for average healing times: TFT plus one drop daily of rHu IFN-alpha 2 arg (30 million iu/ml): 3.3 days, TFT plus rHu IFN-gamma (30 million iu/ml): 3.9 days, TFT plus a mixture of alpha plus gamma (0.3 million iu/ml each): 6.1 days, TFT plus a mixture of alpha plus gamma (1.5 million iu/ml each): 3.3 days. High-titer gamma interferon did not significantly differ from high-titer alpha interferon in the combination therapy of dendritic keratitis. A mixture of alpha plus gamma at a moderate titer (1.5 million iu/ml each) was as effective as a high-titer mono-preparation. Adding a low-titer interferon mixture gave no better therapeutic results than antiviral monotherapy. Thus it seems possible to save about 90% of interferon commonly used in the combination therapy of dendritic keratitis by applying a mixture of different suitable interferons instead of interferon monospecies.
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PMID:The potency of interferon-alpha 2 and interferon-gamma in a combination therapy of dendritic keratitis. A controlled clinical study. 303 Jun 50

No statistical difference was found in both partial and complete healing time in acute epithelial herpetic keratitis between the ACV-recombinant human alpha 2 IFN (both "eyedrops" and "eyerods") and Buffy coat human leucocyte alpha IFN. A highly significant difference was found in both partial and complete healing time between the ACV-IFN combination versus the ACV-Placebo combination. The combination of ACV and recombinant human alpha 2 arg IFN is a potent anti-herpetic treatment.
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PMID:Combination therapy of recombinant human alpha 2 interferon and acyclovir in the treatment of herpes simplex keratitis. 390 58

Sclerosing keratitis is the major cause of blindness due to onchocerciasis which results from chronic infection with the filarial parasite Onchocerca volvulus. Using a murine model of onchocercal sclerosing keratitis, we have demonstrated previously that predominantly (> 85%) CD3 + /CD4+ T-cells as well as the IL-2 receptor bearing cells infiltrate into the cornea in vivo during development and progress of the disease. The identification of CD4+ subsets TH1 and TH2 based on the cytokine secretion patterns of murine T-lymphocytes has been useful for understanding the immune basis of resistance and pathogenesis in murine models of several parasitic diseases. The present investigation was carried out to demonstrate whether the local immune response at the corneal lesion due to onchocercal interstitial keratitis correlated with such distinct patterns of cytokine production. For that purpose, mRNA was extracted separately from corneas obtained from the diseased eyes and the normal eyes of A/J mice with onchocercal interstitial keratitis, reverse transcribed and amplified by the polymerase chain reaction with four different cytokine specific primers. In corneas obtained from the eyes affected with onchocercal interstitial keratitis, mRNAs coding for IL-4 and IL-5 were up-regulated compared to the normal eyes having no lesions from the same animals. However, the levels of mRNAs for IL-2 and IFN gamma were found to be the same in the diseased and normal eyes. Taken together, these data suggest that IL-4 and IL-5 producing TH2-lymphocytes are active at the corneal lesion due to onchocercal interstitial keratitis.
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PMID:In vivo molecular analysis of cytokines in a murine model of ocular onchocerciasis. I. Up-regulation of IL-4 and IL-5 mRNAs and not IL-2 and IFN gamma mRNAs in the cornea due to experimental interstitial keratitis. 903 Sep 83

The role of immunologic factors in the development of ophthalmic pathologies in persons infected by hepatitis B virus (HBV) affecting the liver or in asymptomatic virus carriers (a total of 285 persons, 328 eyes) was studied. The deficit of CD3 and CD4 cells, gammopathy, increased levels of circulating immune complexes and of TNF-alpha in the serum; the deficit of IgA and an enhanced secretion of IgG in the lachrymal fluid; as well as a weakened ability of the local and systematic production of IFN-alpha were typical for a majority of patients. The most profound changes were detected in cases of uveitis; apart from the above mentioned, an increase of the CD4/CD8 index as well as of organ-specific and inter-organ immunization was found. The cases of keratitis (92% of the stromal type) were distinguished through a hypersecretion of TNF-alpha both in the serum and in the lachrymal fluid. Complicated cataracts were observed mainly in convalescents or in asymptomatic virus carriers; immune disorders were less seldom encountered in this category, as compared to the cases of eye inflammations, and basically they were local. The obtained data were considered in treatment. Imunofan, when added to the traditional therapy (symptomatic and corticosteroid one), activated the local and systematic antiviral immunity, suppressed the production of pro-viral cytokines and reduced the autoimmune reactions. As a result of this, the treatment time, the frequency rate of relapses as well as the number of anti-inflammatory and postoperative (in cataracts) complications decreased. The study results are indicative of that the immunopathological reactions, which are typical of HBV patients, can be detected at the ocular level and they can provoke ophthalmic pathologies. The nature, severity and relation between the local and systematic immune disorders predetermine, to a considerable extent, the development of an eye disease and its severity. The treatment (and prophylaxis) of HBV-associated ophthalmic pathologies require an obligatory usage of immunity-correcting means and clinical-and-immunological monitoring.
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PMID:[The role of immunopathological reactions in the development of eye diseases in persons infected by hepatitis B virus and the efficiency of immuno-correcting therapy]. 1280 Apr 83

In this study, we assessed the efficacy of the specific knockdown of matrix metalloprotein-9 (MMP-9) in vitro and in vivo using short hairpin RNA (shRNA) against MMP-9. Two plasmids were generated encoding shRNA (pshRNA) targeted against two distinct MMP-9 gene sequences. Transfection of these pshMMP-9s could be shown to specifically inhibit MMP-9 expression both in vivo and in vitro. The effect occurred in vitro both in cells that endogenously produce MMP-9 and in cells exogenously transfected with an MMP-9-encoding plasmid. Using an in vivo transfection approach, the pshMMP- 9 was also effective at inhibiting MMP-9 protein expression in the mouse cornea. pshMMP-9s were also tested against herpes simplex virus (HSV) in the cornea. Delivery of the pshMMP-9 stopped angiogenesis and decreased the severity of herpetic keratitis. However, interferon-alpha (IFN-alpha) and IFN- beta induced by pshRNA might also contribute to inhibition of herpetic simplex keratitis (HSK) in the cornea.
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PMID:Blocking mouse MMP-9 production in tumor cells and mouse cornea by short hairpin (sh) RNA encoding plasmids. 1598 22

The paper presents data on elevated serum and lacrimal fluid alpha- and gamma-interferon (INF) levels in patients with herpetic keratitis (HK) in the course of the disease depending on its clinical form and stage. A more significant increase in the levels of alpha- and gamma-INF was noted in the lacrimal fluid, which was indicative of the important role of local antiherpetic corneal and conjunctival protection. The determination of serum and lacrimal fluid IFN levels in patients with HK may be used to predict the clinical course of the disease.
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PMID:[Imbalance of alpha- and gamma-interferon levels in patients with herpetic keratitis]. 1875 15


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