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Cytokine ; 148: 155599, 2021 12.
Article in English | MEDLINE | ID: mdl-34103211

ABSTRACT

Interleukin-15 (IL-15) is a pleiotropic cytokine that plays pivotal roles in innate and adaptive immunity. It is also a promising cytokine for treating cancer. Despite growing interest in its use as an immunotherapeutic, its safety and immunological effects in dogs have not been reported. In this study, healthy dogs were given recombinant canine IL-15 (rcIL-15) intravenously at a daily dose of 20 µg/kg for 8 days and monitored for 32 days to determine the safety and immunological effects of rcIL-15. The repeated administration of rcIL-15 was well tolerated, did not cause any serious side effects, and promoted the selective proliferation and activation of canine anti-cancer effector cells, including CD3+CD8+ cytotoxic T lymphocytes, CD3+CD5dimCD21-, and non-B/non-T NK cell populations, without stimulating Treg lymphocytes. The rcIL-15 injections also stimulated the expression of molecules and transcription factors associated with the activation and effector functions of NK cells, including CD16, NKG2D, NKp30, NKp44, NKp46, perforin, granzyme B, Ly49, T-bet, and Eomes. These results suggest that rcIL-15 might be a valuable therapeutic adjuvant to improve immunity against cancer in dogs.


Subject(s)
Interleukin-15/adverse effects , Interleukin-15/immunology , Recombinant Proteins/adverse effects , Recombinant Proteins/immunology , Animals , Antigens, CD/metabolism , Cell Proliferation/drug effects , Cytotoxicity, Immunologic/drug effects , Dogs/blood , Forkhead Transcription Factors/metabolism , Gene Expression Regulation/drug effects , Granzymes/metabolism , Humans , Interleukin-15/administration & dosage , Interleukin-15/toxicity , K562 Cells , Killer Cells, Natural/metabolism , Leukocyte Count , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Lymphocyte Subsets/drug effects , Lymphocyte Subsets/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Recombinant Proteins/administration & dosage , Recombinant Proteins/toxicity , T-Box Domain Proteins/metabolism
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