PMID- 34305950
OWN - NLM
STAT- MEDLINE
DCOM- 20220104
LR  - 20220104
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - IL-10-Dependent Amelioration of Chronic Inflammatory Disease by Microdose 
      Subcutaneous Delivery of a Prototypic Immunoregulatory Small Molecule.
PG  - 708955
LID - 10.3389/fimmu.2021.708955 [doi]
LID - 708955
AB  - One of the interventional strategies to reestablish the immune 
      effector/regulatory balance, that is typically altered in chronic inflammatory 
      diseases (CID), is the reinforcement of endogenous immunomodulatory pathways as 
      the one triggered by interleukin (IL)-10. In a recent work, we demonstrated that 
      the subcutaneous (sc) administration of an IL-10/Treg-inducing small 
      molecule-based formulation, using a repetitive microdose (REMID) treatment 
      strategy to preferentially direct the effects to the regional immune system, 
      delays the progression of atherosclerosis. Here we investigated whether the same 
      approach using other IL-10-inducing small molecule, such as the safe, 
      inexpensive, and widely available polyphenol curcumin, could induce a similar 
      protective effect in two different CID models. We found that, in apolipoprotein E 
      deficient mice, sc treatment with curcumin following the REMID strategy induced 
      atheroprotection that was not consequence of its direct systemic lipid-modifying 
      or antioxidant activity, but instead paralleled immunomodulatory effects, such as 
      reduced proatherogenic IFNgamma/TNFalpha-producing cells and increased atheroprotective 
      FOXP3(+) Tregs and IL-10-producing dendritic and B cells. Remarkably, when a 
      similar strategy was used in the neuroinflammatory model of experimental 
      autoimmune encephalomyelitis (EAE), significant clinical and histopathological 
      protective effects were evidenced, and these were related to an improved 
      effector/regulatory cytokine balance in restimulated splenocytes. The essential 
      role of curcumin-induced IL-10 for neuroprotection was confirmed by the complete 
      abrogation of the clinical effects in IL-10-deficient mice. Finally, the 
      translational therapeutic prospection of this strategy was evidenced by the 
      neuroprotection observed in mice starting the treatment one week after disease 
      triggering. Collectively, results demonstrate the power of a simple natural 
      IL-10-inducing small molecule to tackle chronic inflammation, when its classical 
      systemic and direct pharmacological view is shifted towards the targeting of 
      regional immune cells, in order to rationally harness its immunopharmacological 
      potential. This shift implies that many well-known IL-10-inducing small molecules 
      could be easily reformulated and repurposed to develop safe, innovative, and 
      accessible immune-based interventions for CID.
CI  - Copyright (c) 2021 Tabares-Guevara, Jaramillo, Ospina-Quintero, Piedrahita-Ochoa, 
      Garcia-Valencia, Bautista-Erazo, Caro-Gomez, Covian, Retamal-Diaz, Duarte, 
      Gonzalez, Bueno, Riedel, Kalergis and Ramirez-Pineda.
FAU - Tabares-Guevara, Jorge H
AU  - Tabares-Guevara JH
AD  - Grupo Inmunomodulacion (GIM), Instituto de Investigaciones Medicas, Facultad de 
      Medicina, Corporacion Academica para el Estudio de Patologias Tropicales (CAEPT), 
      Universidad de Antioquia, Medellin, Colombia.
FAU - Jaramillo, Julio C
AU  - Jaramillo JC
AD  - Grupo Inmunomodulacion (GIM), Instituto de Investigaciones Medicas, Facultad de 
      Medicina, Corporacion Academica para el Estudio de Patologias Tropicales (CAEPT), 
      Universidad de Antioquia, Medellin, Colombia.
FAU - Ospina-Quintero, Laura
AU  - Ospina-Quintero L
AD  - Grupo Inmunomodulacion (GIM), Instituto de Investigaciones Medicas, Facultad de 
      Medicina, Corporacion Academica para el Estudio de Patologias Tropicales (CAEPT), 
      Universidad de Antioquia, Medellin, Colombia.
FAU - Piedrahita-Ochoa, Christian A
AU  - Piedrahita-Ochoa CA
AD  - Grupo Inmunomodulacion (GIM), Instituto de Investigaciones Medicas, Facultad de 
      Medicina, Corporacion Academica para el Estudio de Patologias Tropicales (CAEPT), 
      Universidad de Antioquia, Medellin, Colombia.
FAU - Garcia-Valencia, Natalia
AU  - Garcia-Valencia N
AD  - Grupo Inmunomodulacion (GIM), Instituto de Investigaciones Medicas, Facultad de 
      Medicina, Corporacion Academica para el Estudio de Patologias Tropicales (CAEPT), 
      Universidad de Antioquia, Medellin, Colombia.
FAU - Bautista-Erazo, David E
AU  - Bautista-Erazo DE
AD  - Grupo Inmunomodulacion (GIM), Instituto de Investigaciones Medicas, Facultad de 
      Medicina, Corporacion Academica para el Estudio de Patologias Tropicales (CAEPT), 
      Universidad de Antioquia, Medellin, Colombia.
FAU - Caro-Gomez, Erika
AU  - Caro-Gomez E
AD  - Grupo Inmunomodulacion (GIM), Instituto de Investigaciones Medicas, Facultad de 
      Medicina, Corporacion Academica para el Estudio de Patologias Tropicales (CAEPT), 
      Universidad de Antioquia, Medellin, Colombia.
FAU - Covian, Camila
AU  - Covian C
AD  - Millennium Institute on Immunology and Immunotherapy, Departamento de Genetica 
      Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia 
      Universidad Catolica de Chile, Santiago, Chile.
FAU - Retamal-Diaz, Angello
AU  - Retamal-Diaz A
AD  - Millennium Institute on Immunology and Immunotherapy, Departamento de Genetica 
      Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia 
      Universidad Catolica de Chile, Santiago, Chile.
FAU - Duarte, Luisa F
AU  - Duarte LF
AD  - Millennium Institute on Immunology and Immunotherapy, Departamento de Genetica 
      Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia 
      Universidad Catolica de Chile, Santiago, Chile.
FAU - Gonzalez, Pablo A
AU  - Gonzalez PA
AD  - Millennium Institute on Immunology and Immunotherapy, Departamento de Genetica 
      Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia 
      Universidad Catolica de Chile, Santiago, Chile.
FAU - Bueno, Susan M
AU  - Bueno SM
AD  - Millennium Institute on Immunology and Immunotherapy, Departamento de Genetica 
      Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia 
      Universidad Catolica de Chile, Santiago, Chile.
FAU - Riedel, Claudia A
AU  - Riedel CA
AD  - Departamento de Ciencias Biologicas, Facultad de Ciencias de la Vida, Millennium 
      Institute on Immunology and Immunotherapy, Universidad Andres Bello, Santiago, 
      Chile.
FAU - Kalergis, Alexis M
AU  - Kalergis AM
AD  - Millennium Institute on Immunology and Immunotherapy, Departamento de Genetica 
      Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia 
      Universidad Catolica de Chile, Santiago, Chile.
AD  - Departamento de Endocrinologia, Escuela de Medicina, Facultad de Medicina, 
      Pontificia Universidad Catolica de Chile, Santiago, Chile.
FAU - Ramirez-Pineda, Jose R
AU  - Ramirez-Pineda JR
AD  - Grupo Inmunomodulacion (GIM), Instituto de Investigaciones Medicas, Facultad de 
      Medicina, Corporacion Academica para el Estudio de Patologias Tropicales (CAEPT), 
      Universidad de Antioquia, Medellin, Colombia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210708
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Apolipoproteins E)
RN  - 0 (Immunomodulating Agents)
RN  - 0 (Lipids)
RN  - 130068-27-8 (Interleukin-10)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/physiology
MH  - Atherosclerosis/prevention & control
MH  - Chronic Disease
MH  - Curcumin/*administration & dosage/pharmacology
MH  - Immunomodulating Agents/*administration & dosage
MH  - Inflammation/*prevention & control
MH  - Interleukin-10/*physiology
MH  - Lipids/blood
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuroprotection
PMC - PMC8297659
OTO - NOTNLM
OT  - Interleukin-10
OT  - atherosclerosis
OT  - chronic inflammatory disease
OT  - curcumin
OT  - experimental autoimmune encephalomyelitis
OT  - immune regulation
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/07/27 06:00
MHDA- 2022/01/05 06:00
PMCR- 2021/01/01
CRDT- 2021/07/26 06:24
PHST- 2021/05/13 00:00 [received]
PHST- 2021/06/24 00:00 [accepted]
PHST- 2021/07/26 06:24 [entrez]
PHST- 2021/07/27 06:00 [pubmed]
PHST- 2022/01/05 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.708955 [doi]
PST - epublish
SO  - Front Immunol. 2021 Jul 8;12:708955. doi: 10.3389/fimmu.2021.708955. eCollection 
      2021.