Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 1, or cellular, immune response is characterized by overproduction of TNF-alpha, IFN-gamma, IL-1, IL-2 and IL-8 and is the underlying immune mechanism of psoriasis, alopecia areata, rheumatoid arthritis, Crohn's disease, multiple sclerosis, insulin-dependent diabetes mellitus and experimental autoimmune uveitis (EAU). Type 2 immune response is seen in antibody-mediated autoimmune diseases. Based on the pharmacokinetic effects of cetirizine and allopurinol, this paper introduces these two safe and inexpensive drugs as novel potential agents against cell-mediated autoimmune disorders. Cetirizine, supposed to inhibit DNA binding activity of NF-kappa B, inhibits the expression of adhesion molecules on immunocytes and endothelial cells and the production of IL-8 and LTB4, two potent chemoattractants, by immune cells. It induces the release of PGE2, a suppressor of antigen presentation and MHC class II expression, from monocyte/macrophages and reduces the number of tryptase positive mast cells in inflammation sites. Tryptase is a chemoattractant, generates kinins from kininogen, activates mast cells, triggers maturation of dendritic cells and stimulates the release of IL-8 from endothelial cells and the production of Th1 lymphokines by mononuclear immunocytes. Allopurinol is a free radical scavenger, suppresses the production of TNF-alpha and downregulates the expression of ICAM-1 and P2X(7) receptors on monocyte/macrophages. ICAM-1 serves as a ligand for LFA-1 (on T lymphocytes), allowing proper antigen presentation. P2X(7) receptors are thought to be involved in IL-1beta release, mitogenic stimulation of T lymphocytes and the probable cytoplasmic communication between macrophages and lymphocytes at inflammation sites. Allopurinol was markedly more effective than prednisolone in treating experimental autoimmune uveitis and in combination with cyclosporine suppressed the inflammatory reaction of this condition more effectively than either agent alone. As allopurinol is a competitive inhibitor of xanthine oxidase and decreases serum levels of uric acid, which is protective against multiple sclerosis, it should preferably be coadministered with uric acid precursors in the treatment of this condition. Cetirizine and allopurinol may prove of benefit in the treatment of various cellular autoimmune disorders.
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PMID:Cetirizine and allopurinol as novel weapons against cellular autoimmune disorders. 1503 12

Cetirizine has been demonstrated able of reducing nasal inflammatory infiltration in children with allergic rhinitis and cytokine production in in vitro studies. The aim of this double-blind, placebo-controlled, and randomized study was to evaluate cytokine pattern and inflammatory cells in children with perennial allergic rhinitis, before and after treatment with cetirizine or placebo. Twenty children with perennial allergic rhinitis were evaluated, 13 males and 7 females (mean age 13.4 years). Inflammatory cells and cytokines were evaluated by scraping and nasal lavage, before and after 2-weeks administration of cetirizine or placebo. IL4 and IL8 were measured by immunoassay and inflammatory cells were counted by conventional staining. Cetirizine treatment induced a significant decrease of IL4 (p<0.01) and IL8 levels (p=0.01). A significant reduction of the inflammatory cells was detected in actively-treated children, both concerning neutrophils and eosinophils (p<0.01). Moreover, cetirizine significantly reduced nasal obstruction score (p=0.007). This study shows the cetirizine effectiveness in exerting anti-inflammatory activity by modulating cytokine pattern and by reducing inflammatory infiltration in children with perennial allergic rhinitis.
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PMID:Cetirizine reduces cytokines and inflammatory cells in children with perennial allergic rhinitis. 1532 7

To investigate the effect of cetirizine hydrochloride on the expression of neurokinin 1 receptor (NK-1R) and cytokines production induced by substance P (SP) in HaCaT cells (a human epidermal keratinocyte cell line) and dermal fibroblasts. The effect of cetirizine on the expression of NK-1R protein was detected by flow cytometry and Western blotting analysis. The modulation of cetirizine on the production of interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6 and IL-8 in HaCaT cells and fibroblasts was measured by ELISA. The results showed that cetirizine significantly inhibited the expression of NK-1R in HaCaT cells and fibroblasts. SP induced the production of IFN-gamma, IL-1beta and IL-8 in both cell types. Cetirizine 1-100 micromol x L(-1) inhibited SP-induced IL-1beta and IL-8 production in HaCaT cells and fibroblasts, while had no effect on the production of IFN-gamma in both cells. Both SP and cetirizine had no effect on the secretion of IL-6 in HaCaT cells and fibroblasts. These findings suggest that cetirizine may be involved in the treatment of SP-induced skin inflammation by inhibiting the expression of substance P receptor and regulation the production of IL-1beta and IL-8 in epidermal keratinocyte and dermal fibroblasts.
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PMID:[Effect of cetirizine hydrochloride on the expression of substance P receptor and cytokines production in human epidermal keratinocytes and dermal fibroblasts]. 1866

Recent studies suggest that several second-generation antihistamines can modulate various inflammatory reactions besides their H(1)-receptor antagonism. The antihistamine cetirizine is a racemic mixture of levocetirizine and dextrocetirizine. The aim of this study was to investigate the effects of these two antihistamines (cetirizine and levocetirizine) on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-8 secretion in A549 human airway epithelial cells. A549 cells were preincubated with cetirizine (0.1, 1, 2.5, 5, and 10 microM) or levocetirizine (0.1, 1, 2.5, 5, and 10 microM) individually for 16 hours and were then stimulated with IL-1beta for 8 hours. The levels of GM-CSF and IL-8 in cultured supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Our data showed that cetirizine (5 and 10 microM) and levocetirizine (2.5, 5, and 10 microM) significantly suppressed GM-CSF secretion from A549 cells stimulated with IL-1beta (p<0.05). Cetirizine (10 microM) and levocetirizine (5 and 10 microM) significantly suppressed IL-8 secretion after A549 was stimulated. The suppressive effect was comparable between levocetirizine, 2.5 microM, and cetirizine, 5 microM, as well as levocetirizine, 5 microM, and cetirizine, 10 microM. Moreover, levocetirizine, 5 microM, was better than cetirizine, 5 microM, on suppressing IL-8 secretion, but such a difference did not appear in other conditions. Our results suggest that cetirizine and levocetirizine at higher concentrations can reduce the release of GM-CSF and IL-8 from A549 cells stimulated with IL-1beta. These observations indicate that the two second-generation antihistamines may exert anti-inflammatory effects beyond histamine H(1)-receptor antagonist, and levocetirizine plays a major role in terms of this activity.
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PMID:Influence of cetirizine and levocetirizine on two cytokines secretion in human airway epithelial cells. 1892 57

We have planned to demonstrate histopathologic effects of mid- or long-term oral use of desloratadine and cetirizine HCl molecules on middle ear mucosa of rats. Thirty-six rats were randomized equally into six groups. Desloratadine groups received once daily doses of 1 mg/ml desloratadine for 30 (D30 Group) or 60 (D60 Group) days. The Cetirizine study groups were given once daily doses of 1 mg/ml cetirizine for 30 (S30 Group) or 60 (S60 Group) days. Control groups were given 2 cc physiologic saline using orogastric gavage method through a 12 G gavage catheter for 30 (K30 Group) or 60 (K60) days. At the end of 30 days, D30, S30 and K30 Groups were sacrificed. Tissue samples harvested from groups were evaluated between 1 and 4 Grades for histological characteristics of middle ear canal, eardrum, middle ear epithelium and connective tissue, edema, vascular congestion and inflammatory cells. In the control group no pathological finding was encountered in rats sacrificed on 30 and 60 days. No statistical difference was observed when groups were compared on external ear epithelial tissue, external ear sebaceous gland, middle ear inflammation, and middle ear capillary dilatation both on 30 and 60 days. Tympanic membrane collagen was more evident in D30 and D60 groups when compared with C30 and C60 groups. Comparison of histopathological grading results between 30 and 60 days revealed no significant changes. In conclusion, oral intake of cetirizine and desloratadine preparations has effects of tympanic membrane collagen, degrees of edema and vascular congestion being more prominent with desloratadine molecule.
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PMID:Effects of oral intake of cetirizine HCl and desloratadine molecules on the middle ear mucosa: an experimental animal study. 2452