Interferon mucosa

Both interferon-a and - 3 have been shown to be absorbed across the rectal mucosa when given with the fatty acid linolenic acid as mixed micelles. In the absence of a permeation enhancer, rectally administered interferons (165 aa) do not achieve detectable levels in blood nor lymph. With 0.56% linolenic acid, a significant degree of lymphatic absorption of interferon-a and -P was detected [20]. The rectally absorbed interferon first distributes into the lymphatics, and interferon concentration is much higher in lymph than... 

Nasal mucus. The nasal mucus protects the body against airborne substances. Nasal mucus consists of mucopolysaccharides complexed with sialic acid, sloughed epithelial cells, bacteria, water (95 percent), glycoproteins and lipids (0.5 to 5 percent), mineral salts (0.5 to 1 percent), and free proteins (albumin, immunoglobulins, lysozyme, interferon, lactoferin, etc., 1 percent).13 45 111 112 The surface pH of the nasal mucosa is 5.5 to 6.5.113... 

Nilsen EM, Lundin KE, Krajci P, Scott H, Sollid LM, Brandtzaeg P. Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Th 1 or ThO profile dominated by interferon gamma. Gut 1995 37 766-776. 

Causes The following causes are seen as being responsible for an acquired immune deficiency syndrome in liver cirrhosis (B.A. Runyon, 1995) (i.) hypofunction of the RES (a decrease in the filter or clearance function and phagocytosis capacity as well as reduced formation of immune modulators) (s. p. 65), (2.) reduction in hepatic synthesis of opsonins (s. p. 66), (3.) compromised function of leucocytes, (4.) impaired proliferation and activation of T lymphocytes, and (5.) increased mucosa permeability to bacteria. Both bacteria and bacterial lipopolysaccharides enter the organism in large numbers. They are responsible for increased serum levels of the cytokines (e. g. interleukins 1 and 6, TNF, y-interferon), and there is increased production of these substances together with their reduced breakdown in the cirrhotic liver. Cytokines are formed in the monocytes of blood and in the mononuclear cells of various organs (above all in ascites). 

Bentley AM, Hamid Q, Robinson DS, et al. Prednisolone treatment in asthma. Reduction in the numbers of eosmophils, T cells, tryptase-only positive mast ceils, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa. Am J Respir Crit Care Med 1996 153 551-6. 

The combined effect of (3-CyD with absorption enhancers such as sodium glycocholate or Azone on the nasal absorption of human fibroblast interferon- 3 in powder form in rabbits has been described. HP- 3-CyD was useful as a biocompatible solubilizer for lipophilic absorption enhancers involved in the nasal preparations of peptides.When insuUn was admiifistered nasally to rats, simultaneous use of an oily penetration enhancer, HPE-101, (l-[2-(decylthio)-ethyl]azacyclopentane-2-one) or oleic acid solubilized in HP-(3-CyD showed a marked increase in serum immuno-reactive insulin levels and marked hypoglycemic (Figure 40.11). The potentiation of the enhancing effect of HPE-101 by HP-(3-CyD can be explained by the facilitated transfer of HPE-101 into the nasal mucosa. Studies on the release of membrane proteins and scanifing electron microscopic observations of rat nasal mucosa indicated that the local mucosal damage due to the combination with HP- 3-CyD may not be serious obstacles to their safe use. 

Potential immunologic mechanisms include both autoimmune and nonautoimmune phenomena. Autoimmunity may be directed against mucosal epithelial cells or against neutrophil cytoplasmic elements. Some patients with IBD have abnormal structural features for colonic epithelial cells even in the absence of active disease. Autoantibodies to these structures have been reported. Also, antineutrophil cytoplasmic antibodies are found in a high percentage of patients with ulcerative colitis (70%) and much less frequently with Crohn s disease. Presence of antineutrophil cytoplasmic antibodies in left-sided ulcerative colitis is associated with resistance to medical therapy. Dysregulation of cytokines is a component of IBD. Specifically, Thi cytokine activity (which enhances cell-mediated immunity and suppresses humoral immunity) is excessive with Crohn s disease, whereas Th2 cytokine activity (which inhibits cell-mediated immunity and enhances humoral immunity) is excessive with ulcerative colitis. The result is that patients have inappropriate T-cell responses to antigens from their own intestinal microflora. Expression of interferon-y (a Thi cytokine) in intestinal mucosa of diseased patients is increased, while interleukin-4 (a Th2 cytokine) is reduced. ... 

Other routes of administration have been evaluated, such as inhalation, intrale-sional, intranasal, intraperitoneal, intraventricular, and intraocular rates, in clinical studies. For the most part, these alternative routes were attempts to improve the delivery of interferon to sites not easily accessible via the systemic circulation. These dosing strategies have provided adequate concentrations of interferon in cerebrospinal fluid, lymph, nasal mucosa, and peritoneal fluid, but have not led to clinical success, undoubtedly reflecting the lack of understanding of the inherent mechanism of interferon action [164]. 

Recent reports demonstrate that T cells (Thl/Tcl) from the bronchial mucosa of patients with COPD predominantly express interferon-y (IFNy) and the... 

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