PMID- 33790106
OWN - NLM
STAT- MEDLINE
DCOM- 20211108
LR  - 20240226
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 44
IP  - 4
DP  - 2021
TI  - The Optimal Dose of Tacrolimus in Combination Therapy with an Anti-TNFalpha Antibody 
      in a Mouse Colitis Model.
PG  - 564-570
LID - 10.1248/bpb.b20-00916 [doi]
AB  - An attempt to use combination therapy with anti-tumor necrosis factor alpha (TNFalpha) 
      antibodies and tacrolimus (TAC) has been tried to induce remission in ulcerative 
      colitis (UC). However, the optimal dose of TAC in combination therapy with 
      anti-TNFalpha antibodies (TAC + anti-TNFalpha therapy) remains unclear. We examined the 
      efficacy of various doses of TAC + anti-TNFalpha therapy in a mouse colitis model. 
      Dextran sulfate sodium induced colitis model mice were divided into an anti-TNFalpha 
      antibody monotherapy group and the groups that received various doses of 
      TAC + anti-TNFalpha therapy. The nuclear factor expression of activated T-cells, 
      cytoplasmic 1 (NFATc1) in the nuclei and the mRNA expression of inflammatory 
      cytokines were assessed by immunohistochemistry and RT-PCR, respectively. The 
      serum anti-TNFalpha antibody concentration was measured with an enzyme-linked 
      immunosorbent assay. The colon length and histological severity were 
      significantly improved in the groups that received any dose of TAC + anti-TNFalpha 
      therapy. The nuclear expression of NFATc1 was inversely proportional to the 
      administered doses of TAC. The expression levels of inflammatory cytokines tended 
      to decrease in proportion to the dose of TAC. The serum concentration of 
      anti-TNFalpha antibodies in the high-dose TAC + anti-TNFalpha therapy was significantly 
      higher than those in the other groups. Low-dose TAC exerted its immunosuppressive 
      effect on T-cells, and additionally, high-dose TAC maintained the serum anti-TNFalpha 
      antibody concentration. When administered in combination with anti-TNFalpha 
      antibodies, the dose of TAC should be adjusted according to the disease severity.
FAU - Murakami, Yuki
AU  - Murakami Y
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
FAU - Fujiya, Mikihiro
AU  - Fujiya M
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
AD  - Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical 
      University.
FAU - Konishi, Hiroaki
AU  - Konishi H
AD  - Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical 
      University.
FAU - Isozaki, Shotaro
AU  - Isozaki S
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
FAU - Sugiyama, Yuya
AU  - Sugiyama Y
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
FAU - Kobayashi, Yu
AU  - Kobayashi Y
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
FAU - Sasaki, Takahiro
AU  - Sasaki T
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
FAU - Kunogi, Takehito
AU  - Kunogi T
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
FAU - Takahashi, Keitaro
AU  - Takahashi K
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
FAU - Ando, Katsuyoshi
AU  - Ando K
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
FAU - Ueno, Nobuhiro
AU  - Ueno N
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
FAU - Kashima, Shin
AU  - Kashima S
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
FAU - Moriichi, Kentaro
AU  - Moriichi K
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
FAU - Tanabe, Hiroki
AU  - Tanabe H
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
FAU - Okumura, Toshikatsu
AU  - Okumura T
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*administration & dosage/blood
MH  - Colitis/chemically induced/*drug therapy/immunology/pathology
MH  - Colon/drug effects/immunology/pathology
MH  - Cytokines/*antagonists & inhibitors/genetics/immunology
MH  - Dextran Sulfate
MH  - Disease Models, Animal
MH  - Drug Therapy, Combination
MH  - Immunosuppressive Agents/*administration & dosage
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Tacrolimus/*administration & dosage
MH  - Mice
OTO - NOTNLM
OT  - anti-tumor necrosis factor alpha antibody
OT  - combination therapy
OT  - refractory ulcerative colitis
OT  - remission induction therapy
OT  - tacrolimus
EDAT- 2021/04/02 06:00
MHDA- 2021/11/09 06:00
CRDT- 2021/04/01 05:52
PHST- 2021/04/01 05:52 [entrez]
PHST- 2021/04/02 06:00 [pubmed]
PHST- 2021/11/09 06:00 [medline]
AID - 10.1248/bpb.b20-00916 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2021;44(4):564-570. doi: 10.1248/bpb.b20-00916.