Aim: To determine pro-inflammatory cytokine secretion from human corneas with different pathology and to establish whether cytokine profile influences corneal graft outcome.
Method: Secretion of both ...proinflammatory cytokine interleukin (IL)-1α and tumor necrosis factor (TNF)-α was measured after cultivation of 47 corneas collected from corneal graft recipients suffering from different corneal diseases. Non-inflammatory corneal diseases were keratoconus (n = 8), keratoglobus (n = 2), bullous keratopathy (n = 11), and Groenouw stromal dystrophy type II (n = 2), whereas inflammatory included vascularized corneal scar (n = 14), rejected graft (n = 6), and corneal ulcer (n = 4). Corneas were cultivated at 37°C for 24 hours and frozen until cytokine detection was measured by immunoassay. Donor corneas unsuitable for transplantation were used as controls (n = 7). Corneal graft recipients were followed at least 18 months and rejection rate was calculated for each group.
Results: The median concentration of IL-1α secreted from corneas of recipients with non-inflammatory diseases was 2.47 pg/mm3 (range, 0.13-9.95). In inflammatory corneal diseases, IL-1α concentration was significantly higher (median, 5.92 pg/mm3; range, 0.48-12.68; P = 0.005). IL-1α production in controls (median, 0.63 pg/mm3; range, 0.36-1.29 pg/mm3) was significantly lower than in inflammatory corneal diseases (P<0.001) and non-inflammatory diseases (P = 0.008). Low level of TNF-α was detected only in 5 cases of vascularized corneal scars, 3 cases of bullous keratopathy, and 3 cases of graft rejection. Rejection rate was significantly higher in inflammatory than in non-inflammatory group (46% vs <10%, respectively, P = 0.008). IL-1α and TNF-α were absent from all patient’s sera, confirming its local intra-ocular production.
Conclusion: Increased production of IL-1α in corneal recipients with inflammatory diseases suggests its role in corneal graft rejection in humans.
We studied IL-1 level in corneal scars with/without neo-vascularization. A total of 27 patients underwent grafting
for corneal scar. Recipients were grouped according to number of vascularized ...quadrants (0 to IV/IV): none (n=12), one
(n=5), two (n=4) and four (n=6). Recipient corneas were collected during surgery and IL-1 measured by immunoassay.
Controls were donor corneas unsuitable for transplantation. Graft rejection rate was calculated for each group.
Mean IL-1 concentration in corneal scars was 63.93 pg/mm3; significantly higher as compared to controls (1.25
2.03 pg/mm3). IL-1 correlated well with amount of blood vessels, except in IV/IV scars: 5.173.65 pg/mm3 for 0/IV;
8.022.51 pg/mm3 for I/IV; 8.273.62 pg/mm3 for II/IV and 4.475.03 pg/mm3 for IV/IV corneal scars. Vascularization
of corneal scar is associated with increased IL-1 level (in all but highly vascularized scars), indicating that
IL-1 promotes early stages of vascularization. Graft rejection rate increases in patients with higher vascularization,
independently of IL-1 level.
We evaluated the role of human gastric pentadecapeptide BPC 157 in corneal epithelial defects healing in rats. 48 rats, in 4 groups (N=12). Total debridement of corneal epithelium preformed ...unilaterally and lesions stained and photographed. Animals medicated as follows: distilled water (control group) or BPC 157 2pg/ml, 2ng/ml, 2μg/ml, 2 drops/rat eye started immediately after injury induction, every 8 hours up to 40 hours (i.e., at 0, 8, 16, 24, 32, 40 h). Lesions were photographed before application or sacrifice (at 48 h). Defect area was analyzed using a special program. Through 48 hour period a steady recovery is noted in controls. Recovery was markedly accelerated in eyes on μg- or ng-topical regimen of BPC 157 (p<0.05). Of note, unlike control lesion present also after 48h, these lesions disappeared already following 40 h (μg) or 48 h (ng) post-injury. BPC 157 was shown to be effective in promoting corneal defects healing in rats. Results were dose dependent.
Summary An association between traumatic stress and cardiovascular disease (CVD) is supported by various epidemiological studies. Platelet activation and binding of activated platelets to leukocytes ...contributes to the pathophysiology of CVD. Evidence of hyperactive sympathetic nervous system, altered expression of platelet α2 -adrenoreceptors (α2 AR), and altered platelet adenylate cyclase activity in patients with posttraumatic stress disorder (PTSD) suggest that platelet reactivity in PTSD may be altered as well. We tested whether platelet reactivity to increasing doses of adenosine-diphosphate (ADP), epinephrine (EPI), or their combination differs between war veterans with PTSD ( n = 15) and healthy controls ( n = 12). For this purpose, citrated whole blood was incubated with increasing concentrations of ADP (0.1, 1, 10 μM), EPI alone (10 nM, 100 nM, 1000 nM), or EPI (10 nM, 100 nM, 1000 nM) in combination with 0.1 μM ADP. A subset of samples was also incubated with 10 μM yohimbine (YOH), α2 AR antagonist, to distinguish receptor-specific effects. Platelet CD62P expression and formation of platelet–leukocyte aggregates (PLA) platelet–monocyte (P–Mo), –lymphocyte (P–Ly), and –neutrophil (P–Ne) aggregates were measured using three-color flow cytometry. Platelet reactivity was higher in war veterans with PTSD when compared to controls, as determined by greater CD62P expression and formation of PLA in response to ADP alone or in combination with EPI. Platelet reactivity also correlated with the severity of PTSD symptoms. Preliminary experiments with YOH indicate that stress-associated EPI elevations may contribute to platelet activation through a α2 AR-dependent mechanism. The enhanced platelet reactivity observed in our study may be the underlying mechanism contributing to the development of CVD in PTSD patients.
Ingestion, digestion and antibody-dependent cell-mediated cytotoxicity (ADCC) of opsonized sheep red blood cells (SRBC), as effector functions of peripheral blood phagocytes, were studied in ...newborns, children, mature and aged adults. All tested functions changed non-synchronously during the lifetime. The ingestion was maximal in newborns, digestion in children and ADCC in mature adults. The ingestion was minimal in aged, but digestion was minimal both in newborns and aged. Such changes of phagocytes' functions could possibly contribute to differences in immune reactions of the age-groups studied. The study indicates the need for establishing age-adjusted normal values for major granulocyte and monocyte effector functions.
