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)

Cytokines are very important in the host defense system, and play a critical role in protection against bacterial and viral infections. Cytokines are also involved in the pathogenesis and development of symptoms in infections. In this article, Helicobacter pylori (H. pylori) infection as bacterial infection, and influenza virus infection, encephalomyocarditis virus (EMCV) infection, and herpes simplex virus (HSV) infection as viral infection are mentioned. In H. pylori infection, various chemokines, especially interleukin (IL)-8, induce inflammatory responses in the gastroduodenal mucosa. Furthermore, IL-6, IL-7, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma are involved in both protection and pathogenesis. In influenza virus infection, IFN-alpha/beta, IFN-gamma, and IL-6 play protective roles. In EMCV infection, IL-6 and TNF-alpha play important roles as a protective and exacerbative factor in acute myocarditis, respectively. Furthermore, in HSV infection, the production of inflammatory cytokines is closely correlated with the pathogenesis of herpetic keratitis, and IFN-gamma plays an important role in enhancing viral clearance from the cornea and trigeminal ganglions.
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PMID:Expression of cytokines in bacterial and viral infections and their biochemical aspects. 1073 41

Cytokine profiles in aqueous humour were studied in relation to corneal disease and subsequent corneal graft survival or rejection. Cytokine levels in samples obtained from eyes with clear grafts (n = 59) were all within the normal range. At the time of penetrating keratoplasty (n = 146), intraocular levels of IL-6 were increased in 38% (50/131), most markedly in eyes with previous allograft failure or herpetic stromal keratitis. The level of IL-10 was increased in 1 eye (n = 144) and of IL-4 and IFN-gamma in none. During rejection (n = 10), the levels of IL-6 in aqueous humour were increased in 75% (3/4), of IL-10 in 50% (3/6), of IL-4 in none (0/4) and of IFN-gamma in 40% (2/5). In conclusion, the levels of total protein and IL-6 were increased prior to penetrating keratoplasty in eyes with previous inflammation. These results could however not predict the final outcome of the graft. Increased intraocular levels of IL-6, IL-10 and IFN-gamma were observed during rejection.
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PMID:Cytokines in aqueous humour and serum before and after corneal transplantation and during rejection. 1082 36

Keratocytes express MHC class I molecules constitutively, and keratocytes stimulated with IFN-gamma express MHC class II molecules. Unstimulated keratocytes constitutively express B7-1 and ICAM-1, as well as low levels of CD40 and 4-1BBL. These findings indicate that keratocytes may deliver both antigen-specific and costimulatory signals to CD4(+) and CD8(+) T cells. To demonstrate that keratocytes expressing B7-1 provide a costimulatory signal to T cells, CD4(+) or CD8(+) mouse T cells were incubated with anti-CD3 mAb and irradiated keratocytes. Enhanced proliferation of both CD4(+) and CD8(+) T cells occurred, and could be inhibited by anti-B7-1 mAb, indicating T cell costimulatory activity by B7-1 on the keratocytes. To demonstrate that keratocytes can deliver an antigen-specific signal, CD4(+) and CD8(+) T cells from herpes-infected mice were incubated with HSV-1-infected, irradiated keratocytes. The resulting T cell proliferation and production of Th1 cytokines (IL-2, IFN-gamma) indicated T cell activation by antigens presented by the infected keratocytes. These results show that keratocytes in the corneal stroma of the mouse can function as antigen-presenting cells and, thus, may play a role in immune-mediated stromal inflammation such as herpetic stromal keratitis.
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PMID:Murine keratocytes function as antigen-presenting cells. 1174 49

Topical application of plasmid DNA encoding IL-12 to the cornea of mice prior to ocular infection with Herpes simplex virus type 1 (HSV) results in diminished corneal immunoinflammatory lesions. Such herpetic stromal keratitis (HSK) reactions in humans represent an important cause of blindness. The effect of IL-12 pretreatment acted via inhibitory effects on corneal neovascularization rather than by inhibiting viral replication or the function of CD4(+) T cells that mediate HSK. The antiangiogenesis induced by IL-12 DNA application was mediated indirectly via the cytokine IFN-gamma and one or both of two chemokine molecules, IP-10 and MIG. Thus IL-12 DNA administration lacked modulatory effects on HSK in GKO mice, indicating the necessary involvement of IFN-gamma induction for antiangiogenesis. In contrast, exposure of GKO mice to IP-10 DNA did suppress the severity of HSK. Furthermore, treatment with specific antisera to IP-10 and MIG in HSV-infected mice abrogated the IL-12-induced inhibitory effect on lesion severity. Taken together, our data indicate that the HSV-induced ocular immunoinflammatory lesions can be modulated by IL-12 and that this effect results from chemokine inhibition of angiogenesis. The use of antiangiogenesis therapy might represent a useful control measure against HSK.
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PMID:IL-12 suppresses the expression of ocular immunoinflammatory lesions by effects on angiogenesis. 1186 84

Pseudomonas aeruginosa keratitis destroys the cornea in susceptible (B6), but not resistant (BALB/c) mice. To determine mechanisms mediating resistance, the role of IFN-gamma, IL-12, and IL-18 was tested in BALB/c mice. RT-PCR analysis detected IFN-gamma mRNA expression levels in cornea that were significantly increased at 1-7 days postinfection. IL-18 mRNA was detected constitutively in cornea and, at 1-7 days postinfection, levels were elevated significantly, while no IL-12 mRNA was similarly detected. To test whether IL-18 contributed to IFN-gamma production, mice were treated with anti-IL-18 mAb. Treatment decreased corneal IFN-gamma mRNA levels, and bacterial load and disease increased/worsened, compared with IgG-treated mice. To stringently examine the role of IFN-gamma in bacterial killing, knockout (-/-) vs wild-type (wt) mice also were tested. All corneas perforated, and bacterial load was increased significantly in -/- vs wt mice. Because disease severity was increased in IFN-gamma(-/-) vs IL-18-neutralized mice, and since IL-18 also induces production of TNF, we tested for TNF-alpha in both groups. ELISA analysis demonstrated significantly elevated corneal TNF-alpha protein levels in IFN-gamma(-/-) vs wt mice after infection. In contrast, RT-PCR analysis of IL-18-neutralized vs IgG-treated infected mice revealed decreased corneal TNF-alpha mRNA expression. Next, to resolve whether TNF was required for bacterial killing, TNF-alpha was neutralized in BALB/c mice. No difference in corneal bacterial load was detected in neutralized vs IgG-treated mice. These data provide evidence that IL-18 contributes to the resistance response by induction of IFN-gamma and that IFN-gamma is required for bacterial killing.
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PMID:IL-18 contributes to host resistance against infection with Pseudomonas aeruginosa through induction of IFN-gamma production. 1202 76

Herpetic stromal keratitis (HSK) and blepharoconjunctivitis in humans are thought partly to result from immunopathological responses to herpes simplex virus type 1 (HSV-1). The corneas of NIH mice were inoculated with HSV-1 (strain McKrae) and mice were examined for signs of disease and infection on days 1, 4, 7, 10, 14 and 21. The eyes and eyelids of infected and control mice were processed for immunohistochemistry and double stained for viral antigens and one of the following cell surface markers (Gr-1, F4/80, CD4, CD8, CD45R or MHC class II) or one of the following cytokines (IL-2, IL-4, IL-6, IL-10, IL-12 or IFN-gamma). All infected mice developed signs of HSK by day 4 and blepharitis by day 7 and these both persisted until day 21, when signs of resolution where apparent. Virus was detected during the first week of infection and became undetectable by day 10. Large numbers of Gr-1(+) cells (neutrophils) infiltrated infected corneas and eyelids in areas of viral antigen and CD4(+) T cells increased significantly in number after virus clearance. In both sites, the predominant cytokines were IL-6, IL-10, IL-12 and IFN-gamma, with few IL-2(+) and IL-4(+) cells. These observations suggest that the immune responses in the cornea are similar to those in the eyelids but, overall, the responses are not clearly characterized as either Th1 or Th2. In both sites, the neutrophil is the predominant infiltrating cell type and is a likely source of the cytokines observed and a major effector of the disease process.
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PMID:Primary herpes simplex virus type 1 infection of the eye triggers similar immune responses in the cornea and the skin of the eyelids. 1207 76

Recently it has been shown that selective subconjunctival macrophage depletion reduced the incidence and severity of stromal herpes simplex virus (HSV) keratitis in mice. In this study, we examined the effect of conjunctival macrophage depletion on the corneal and systemic T-cell-mediated immune response. BALB/c mice were treated with subconjunctival injections of dichloromethylene diphosphonate (Cl2MDP)-liposomes (Cl2MDP-LIP) or phosphate-buffered saline (PBS) 7 and 2 days before corneal infection with 105 plaque-forming units (PFU) of HSV-1 (KOS strain). Interferon (IFN)-gamma, interleukin (IL)-2, and IL-4 production in the cornea was analysed by enzyme-linked immunosorbent assay (ELISA), and cytokine mRNA levels (IFN-gamma, IL-4) were measured by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Cell culture supernatants from submandibular lymph nodes were analysed by ELISA for expression of IFN-gamma, IL-2, and IL-4 and by bioassay for IL-6. The HSV-1-specific proliferative response of lymphocytes from regional lymph nodes and the delayed-type hypersensitivity (DTH) response were tested after corneal infection. Virus-neutralizing antibody titres and HSV-1-specific immunoglobulin G (IgG)2a/IgG1-ratios were measured. Cytokine mRNA expression (IFN-gamma, IL-4) and secretion (IFN-gamma, IL-2, IL-4) in the corneas were decreased after HSV-1 corneal infection in the macrophage-depleted mice. The secretion of IFN-gamma and IL-2 was decreased in the regional lymph nodes from Cl2MDP-LIP-treated animals (P<0.05). Furthermore, Cl2MDP-LIP-treated mice had decreased HSV-1 specific proliferative responses (P<0.05) and DTH response after corneal HSV-1 infection (P<0.05). The virus-neutralizing serum-antibody levels (P<0.05) increased while the HSV-1 specific IgG2a/IgG1-ratio was unaffected after macrophage depletion. Macrophage depletion did not induce a shift between the T helper 1 (Th1) and Th2 response in this HSK model. The data suggest that conjunctival macrophage functions are enhancing the T-cell-mediated immune response after corneal infection. This effect is at least in part responsible for the impaired course of herpetic keratitis after macrophage depletion.
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PMID:Conjunctival macrophage-mediated influence of the local and systemic immune response after corneal herpes simplex virus-1 infection. 1222 70

Herpetic stromal keratitis (HSK) is an immunopathologic disease triggered by infection of the cornea with HSV. Key events in HSK involve the interaction between cornea-infiltrating inflammatory cells and resident cells. This interaction, in which macrophages, producing IL-1 and TNF-alpha, and IFN-gamma-producing Th1 cells play a crucial role, results in the local secretion of immune-modulatory factors and a major influx of neutrophils causing corneal lesions and blindness. The Th1-derived cytokine IL-17 has been shown to play an important role in several inflammatory diseases characterized by a massive infiltration of neutrophils into inflamed tissue. Here we show that IL-17 is expressed in corneas from patients with HSK and that the IL-17R is constitutively expressed by human corneal fibroblasts (HCF). IL-17 exhibited a strong synergistic effect with TNF-alpha on the induction of IL-6 and IL-8 secretion by cultured HCF. Secreted IL-8 in these cultures had a strong chemotactic effect on neutrophils. IL-17 also enhanced TNF-alpha- and IFN-gamma-induced secretion of macrophage-inflammatory proteins 1alpha and 3alpha, while inhibiting the induced secretion of RANTES. Furthermore, considerable levels of IFN-gamma-inducible protein 10 and matrix metalloproteinase 1 were measured in stimulated HCF cultures, while the constitutive secretion of monocyte chemotactic protein 1 remained unaffected. The data presented suggest that IL-17 may play an important role in the induction and/or perpetuation of the immunopathologic processes in human HSK by modulating the secretion of proinflammatory and neutrophil chemotactic factors by corneal resident fibroblasts.
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PMID:IL-17 expression in human herpetic stromal keratitis: modulatory effects on chemokine production by corneal fibroblasts. 1242 73

Recently, prokaryotic DNAs containing unmethylated CpG motifs have been shown to be intrinsically immunostimulatory both in vitro and in vivo, tending to promote Th1-like responses. In contrast, CpG dinucleotides in mammalian DNAs are extensively methylated on cytosines and hence immunologically inert. Since the herpes simplex virus (HSV) genome is unmethylated and G+C rich, we predicted that CpG motifs would be highly prevalent in the HSV genome; hence, we examined the immunostimulatory potential of purified HSV DNA in vitro and in vivo. Mouse splenocyte cultures treated with HSV DNA or HSV-derived oligodeoxyribonucleotides (ODNs) showed strong proliferative responses and production of inflammatory cytokines (gamma interferon [IFN-gamma], tumor necrosis factor [TNF], and interleukin-6 [IL-6]) in vitro, whereas splenocytes treated with mammalian CV-1 DNA or non-CpG ODN did not. After immunization with ovalbumin (OVA), only splenocytes from mice immunized with HSV DNA or HSV-ODN as the adjuvants proliferated strongly and produced typical Th1 responses, including CD8(+) cytotoxic T-lymphocyte responses, upon restimulation with OVA. Furthermore, HSV-ODN synergized with IFN-gamma to induce nitric oxide (NO), IL-6, and TNF production from macrophages. These results demonstrate that HSV DNA and HSV-ODN are immunostimulatory, driving potent Th1 responses both in vitro and in vivo. Considering that HSV DNA has been found to persist in nonneuronal cells, these results fuel speculation that HSV DNA might play a role in pathogenesis, in particular, in diseases like herpes stromal keratitis (HSK) that involve chronic inflammatory responses in the absence of virus or viral antigens.
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PMID:Herpes simplex virus type 1 DNA is immunostimulatory in vitro and in vivo. 1451 63

Pseudomonas aeruginosa (P. aeruginosa) is a common organism associated with bacterial keratitis, especially in those who use extended wear contact lenses. Recent advances in our understanding of host innate and adaptive immune responses to experimental infection have been made using a variety of animal models, including inbred murine models that are classed as resistant (cornea heals) vs. susceptible (cornea perforates). Evidence has been provided that sustained IL-12-driven IFN-gamma production in dominant Th1 responder strains such as C57BL/6 (B6) contributes to corneal destruction and perforation, while IL-18-driven production of IFN-gamma in the absence of IL-12 is associated with bacterial killing and less corneal destruction in dominant Th2 responder strains such as BALB/c. The critical role of IL-1 and chemotactic cytokines such as MIP-2 in PMN recruitment and the critical role of this cell in the innate immune response to bacterial infection is reviewed. Regulation of PMN persistence is also discussed and evidence provided that persistence of PMN in B6 cornea is regulated by CD4+ T cells, while macrophages regulate PMN number in the cornea of BALB/c mice. The studies provide a better understanding of the inflammatory mechanisms that are operative in the cornea after P. aeruginosa challenge and are consistent with long-term goals of providing targets for alternative or adjunctive treatment for this disease. Future studies will be aimed at better defining the role of Toll receptors, neuropeptides (as unconventional modulators of the immune response) and exploitation of disease control by new techniques, such as RNA silencing.
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PMID:Corneal response to Pseudomonas aeruginosa infection. 1476 15


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