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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1996-8-16
|
| pubmed:abstractText |
Cellular IL-10 (cIL-10), the collective term for human and murine IL-10, has both stimulatory and inhibitory effects on diverse cell types, including costimulation of T cell proliferation, chemoattraction of CD8+ T cells, and stimulation of lymphokine-activated killer cell activity. Human IL-10 (hIL-10) differs from its EBV homolog viral IL-10 (vIL-10) by only 16% at the amino acid level; however, vIL-10 shares with cIL-10 predominantly inhibitory effects, such as macrophage deactivation. We administered cIL-10 systemically to mice bearing established (day 7) sarcomas, melanomas, or colorectal carcinomas. At high doses (20 to 60 micrograms/day x 7 days), cIL-10 induced rejection of tumors, delaying tumor outgrowth or resulting in complete cure. Sublethal irradiation (500 rad) of mice prior to tumor inoculation abrogated the IL-10 effect. Cured mice were immune to subsequent rechallenge with 10-fold higher inoculation with the same, but not a different, tumor. IL-12 also has potent antitumor activity and interacts with IL-10 in both complementary and antagonistic ways; co-administration of both cytokines resulted in additive antitumor activity. To compare cIL-10 vs vIL-10 effects in vivo, we engineered CL8-1 melanoma transfectants bearing the vIL-10 or the murine IL-10 (mIL-10) gene. Local secretion of mIL-10 induced rejection of tumors, while vIL-10 resulted in accelerated outgrowth. Subsequent systemic administration of cIL-10 to mice bearing vIL-10-transduced tumors completely reversed the local suppressive effects, leading to rejection, suggesting distinct pathways for cIL-10 and vIL-10 effects. That cIL-10 can stimulate the acquisition of an effective, specific, and long-lived antitumor immune response in murine models and can reverse the local immunosuppressive effects of vIL-10 indicates a potential role for cIL-10 administration in the biologic therapy of cancer and suggests a broader interpretation of IL-10 biology.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0022-1767
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
157
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
231-8
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8683120-Adenocarcinoma,
pubmed-meshheading:8683120-Adjuvants, Immunologic,
pubmed-meshheading:8683120-Animals,
pubmed-meshheading:8683120-Colonic Neoplasms,
pubmed-meshheading:8683120-Drug Synergism,
pubmed-meshheading:8683120-Female,
pubmed-meshheading:8683120-Humans,
pubmed-meshheading:8683120-Immunotherapy, Active,
pubmed-meshheading:8683120-Injections, Intradermal,
pubmed-meshheading:8683120-Interleukin-10,
pubmed-meshheading:8683120-Interleukin-12,
pubmed-meshheading:8683120-Killer Cells, Lymphokine-Activated,
pubmed-meshheading:8683120-Mice,
pubmed-meshheading:8683120-Mice, Inbred C57BL,
pubmed-meshheading:8683120-Models, Immunological,
pubmed-meshheading:8683120-Recombinant Proteins,
pubmed-meshheading:8683120-Sarcoma, Experimental,
pubmed-meshheading:8683120-Spleen
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Systemic administration of cellular IL-10 induces an effective, specific, and long-lived immune response against established tumors in mice.
|
| pubmed:affiliation |
Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, PA 15261, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|