Mucosal delivery of anti-inflammatory IL-1Ra by sporulating recombinant bacteria
<p>Abstract</p> <p>Background</p> <p>Mucosal delivery of therapeutic protein drugs or vaccines is actively investigated, in order to improve bioavailability and avoid side effects associated with systemic administration. Orally administered bacteria, engineered to produ...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2004-10-01
|
| Series: | BMC Biotechnology |
| Online Access: | http://www.biomedcentral.com/1472-6750/4/27 |
| _version_ | 1818808383677923328 |
|---|---|
| author | Ruggiero Paolo Bossù Paola Porzio Stefano Boraschi Diana Tagliabue Aldo |
| author_facet | Ruggiero Paolo Bossù Paola Porzio Stefano Boraschi Diana Tagliabue Aldo |
| author_sort | Ruggiero Paolo |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Mucosal delivery of therapeutic protein drugs or vaccines is actively investigated, in order to improve bioavailability and avoid side effects associated with systemic administration. Orally administered bacteria, engineered to produce anti-inflammatory cytokines (IL-10, IL-1Ra), have shown localised ameliorating effects in inflammatory gastro-intestinal conditions. However, the possible systemic effects of mucosally delivered recombinant bacteria have not been investigated.</p> <p>Results</p> <p><it>B. subtilis </it>was engineered to produce the mature human IL-1 receptor antagonist (IL-1Ra). When recombinant <it>B. subtilis </it>was instilled in the distal colon of rats or rabbits, human IL-1Ra was found both in the intestinal lavage and in the serum of treated animals. The IL-1Ra protein in serum was intact and biologically active. IL-1-induced fever, neutrophilia, hypoglycemia and hypoferremia were inhibited in a dose-dependent fashion by intra-colon administration of IL-1Ra-producing <it>B. subtilis</it>. In the mouse, intra-peritoneal treatment with recombinant <it>B. subtilis </it>could inhibit endotoxin-induced shock and death. Instillation in the rabbit colon of another recombinant <it>B. subtilis </it>strain, which releases bioactive human recombinant IL-1β upon autolysis, could induce fever and eventually death, similarly to parenteral administration of high doses of IL-1β.</p> <p>Conclusions</p> <p>A novel system of controlled release of pharmacologically active proteins is described, which exploits bacterial autolysis in a non-permissive environment. Mucosal administration of recombinant <it>B. subtilis </it>causes the release of cytoplasmic recombinant proteins, which can then be found in serum and exert their biological activity <it>in vivo </it>systemically.</p> |
| first_indexed | 2024-12-18T19:40:41Z |
| format | Article |
| id | doaj.art-8d133980c5ba4665b65fb8d4062b273a |
| institution | Directory Open Access Journal |
| issn | 1472-6750 |
| language | English |
| last_indexed | 2024-12-18T19:40:41Z |
| publishDate | 2004-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biotechnology |
| spelling | doaj.art-8d133980c5ba4665b65fb8d4062b273a2022-12-21T20:55:28ZengBMCBMC Biotechnology1472-67502004-10-01412710.1186/1472-6750-4-27Mucosal delivery of anti-inflammatory IL-1Ra by sporulating recombinant bacteriaRuggiero PaoloBossù PaolaPorzio StefanoBoraschi DianaTagliabue Aldo<p>Abstract</p> <p>Background</p> <p>Mucosal delivery of therapeutic protein drugs or vaccines is actively investigated, in order to improve bioavailability and avoid side effects associated with systemic administration. Orally administered bacteria, engineered to produce anti-inflammatory cytokines (IL-10, IL-1Ra), have shown localised ameliorating effects in inflammatory gastro-intestinal conditions. However, the possible systemic effects of mucosally delivered recombinant bacteria have not been investigated.</p> <p>Results</p> <p><it>B. subtilis </it>was engineered to produce the mature human IL-1 receptor antagonist (IL-1Ra). When recombinant <it>B. subtilis </it>was instilled in the distal colon of rats or rabbits, human IL-1Ra was found both in the intestinal lavage and in the serum of treated animals. The IL-1Ra protein in serum was intact and biologically active. IL-1-induced fever, neutrophilia, hypoglycemia and hypoferremia were inhibited in a dose-dependent fashion by intra-colon administration of IL-1Ra-producing <it>B. subtilis</it>. In the mouse, intra-peritoneal treatment with recombinant <it>B. subtilis </it>could inhibit endotoxin-induced shock and death. Instillation in the rabbit colon of another recombinant <it>B. subtilis </it>strain, which releases bioactive human recombinant IL-1β upon autolysis, could induce fever and eventually death, similarly to parenteral administration of high doses of IL-1β.</p> <p>Conclusions</p> <p>A novel system of controlled release of pharmacologically active proteins is described, which exploits bacterial autolysis in a non-permissive environment. Mucosal administration of recombinant <it>B. subtilis </it>causes the release of cytoplasmic recombinant proteins, which can then be found in serum and exert their biological activity <it>in vivo </it>systemically.</p>http://www.biomedcentral.com/1472-6750/4/27 |
| spellingShingle | Ruggiero Paolo Bossù Paola Porzio Stefano Boraschi Diana Tagliabue Aldo Mucosal delivery of anti-inflammatory IL-1Ra by sporulating recombinant bacteria BMC Biotechnology |
| title | Mucosal delivery of anti-inflammatory IL-1Ra by sporulating recombinant bacteria |
| title_full | Mucosal delivery of anti-inflammatory IL-1Ra by sporulating recombinant bacteria |
| title_fullStr | Mucosal delivery of anti-inflammatory IL-1Ra by sporulating recombinant bacteria |
| title_full_unstemmed | Mucosal delivery of anti-inflammatory IL-1Ra by sporulating recombinant bacteria |
| title_short | Mucosal delivery of anti-inflammatory IL-1Ra by sporulating recombinant bacteria |
| title_sort | mucosal delivery of anti inflammatory il 1ra by sporulating recombinant bacteria |
| url | http://www.biomedcentral.com/1472-6750/4/27 |
| work_keys_str_mv | AT ruggieropaolo mucosaldeliveryofantiinflammatoryil1rabysporulatingrecombinantbacteria AT bossupaola mucosaldeliveryofantiinflammatoryil1rabysporulatingrecombinantbacteria AT porziostefano mucosaldeliveryofantiinflammatoryil1rabysporulatingrecombinantbacteria AT boraschidiana mucosaldeliveryofantiinflammatoryil1rabysporulatingrecombinantbacteria AT tagliabuealdo mucosaldeliveryofantiinflammatoryil1rabysporulatingrecombinantbacteria |