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Effect of alemtuzumab on intestinal intraepithelial lymphocytes and intestinal barrier function in cynomolgus model.

Qu LL, Lyu YQ, Jiang HT, Shan T, Zhang JB, Li QR, Li JS - Chin. Med. J. (2015)

Bottom Line: The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 × 10 8 and 1.35 ± 0.09 × 10 8 , respectively; P < 0.05) and were not fully restored until day 70 after treatment.There were significant differences among four groups considering IELs subtypes.Moreover, the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Institute of General Surgery, Jinling Hospital, Nanjing, Jiangsu 210002, China.

ABSTRACT

Background: Alemtuzumab has been used in organ transplantation and a variety of hematologic malignancies (especially for the treatment of B-cell chronic lymphocytic leukemia). However, serious infectious complications frequently occur after treatment. The reason for increased infections postalemtuzumab treatment is unknown at this stage. We explore the effect of alemtuzumab on intestinal intraepithelial lymphocytes (IELs) and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment.

Methods: Twelve male cynomolguses were randomly assigned to either a treatment or control group. The treatment group received alemtuzumab (3 mg/kg, intravenous injection) while the control group received the same volume of physiological saline. Intestinal IELs were isolated from the control group and the treatment group (on day 9, 35, and 70 after treatment) for counting and flow cytometric analysis. Moreover, intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay.

Results: The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 × 10 8 and 1.35 ± 0.09 × 10 8 , respectively; P < 0.05) and were not fully restored until day 70 after treatment. There were significant differences among four groups considering IELs subtypes. In addition, the proportion of apoptotic IELs after alemtuzumab treatment was significantly higher than in the control group (22.01 ± 3.67 and 6.01 ± 1.42, respectively; P < 0.05). Moreover, the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment.

Conclusions: Alemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model. The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment. Notably, intestinal barrier function may be disrupted after alemtuzumab treatment.

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Gross morphology (a) and histology (b) of cynomolgus treated with physical saline or alemtuzumab. Representative H and E-stained histological sections. The results are representative of those obtained with 3 cynomolguses of each group. Original magnification, ×40.
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Figure 3: Gross morphology (a) and histology (b) of cynomolgus treated with physical saline or alemtuzumab. Representative H and E-stained histological sections. The results are representative of those obtained with 3 cynomolguses of each group. Original magnification, ×40.

Mentions: In the present study, the difference in thickness of the intestinal wall and number of mucosal folds was shown in the ileum of cynomolgus after alemtuzumab treatment [Figure 3a]. The intestine of cynomolgus in the control group had more abundant folds and thicker intestinal wall. However, after being treated for 9 days, the ileums of cynomolgus appeared to have a thinner intestinal wall and the mucosal folds nearly disappeared. On day 35, after alemtuzumab treatment, sporadic mucosal fold emerged, however, the intestinal wall still appeared very thin. As shown in Figure 4a, the ileum showed normal mucosal folds by 70 days after treatment.


Effect of alemtuzumab on intestinal intraepithelial lymphocytes and intestinal barrier function in cynomolgus model.

Qu LL, Lyu YQ, Jiang HT, Shan T, Zhang JB, Li QR, Li JS - Chin. Med. J. (2015)

Gross morphology (a) and histology (b) of cynomolgus treated with physical saline or alemtuzumab. Representative H and E-stained histological sections. The results are representative of those obtained with 3 cynomolguses of each group. Original magnification, ×40.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834783&req=5

Figure 3: Gross morphology (a) and histology (b) of cynomolgus treated with physical saline or alemtuzumab. Representative H and E-stained histological sections. The results are representative of those obtained with 3 cynomolguses of each group. Original magnification, ×40.
Mentions: In the present study, the difference in thickness of the intestinal wall and number of mucosal folds was shown in the ileum of cynomolgus after alemtuzumab treatment [Figure 3a]. The intestine of cynomolgus in the control group had more abundant folds and thicker intestinal wall. However, after being treated for 9 days, the ileums of cynomolgus appeared to have a thinner intestinal wall and the mucosal folds nearly disappeared. On day 35, after alemtuzumab treatment, sporadic mucosal fold emerged, however, the intestinal wall still appeared very thin. As shown in Figure 4a, the ileum showed normal mucosal folds by 70 days after treatment.

Bottom Line: The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 × 10 8 and 1.35 ± 0.09 × 10 8 , respectively; P < 0.05) and were not fully restored until day 70 after treatment.There were significant differences among four groups considering IELs subtypes.Moreover, the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Institute of General Surgery, Jinling Hospital, Nanjing, Jiangsu 210002, China.

ABSTRACT

Background: Alemtuzumab has been used in organ transplantation and a variety of hematologic malignancies (especially for the treatment of B-cell chronic lymphocytic leukemia). However, serious infectious complications frequently occur after treatment. The reason for increased infections postalemtuzumab treatment is unknown at this stage. We explore the effect of alemtuzumab on intestinal intraepithelial lymphocytes (IELs) and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment.

Methods: Twelve male cynomolguses were randomly assigned to either a treatment or control group. The treatment group received alemtuzumab (3 mg/kg, intravenous injection) while the control group received the same volume of physiological saline. Intestinal IELs were isolated from the control group and the treatment group (on day 9, 35, and 70 after treatment) for counting and flow cytometric analysis. Moreover, intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay.

Results: The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 × 10 8 and 1.35 ± 0.09 × 10 8 , respectively; P < 0.05) and were not fully restored until day 70 after treatment. There were significant differences among four groups considering IELs subtypes. In addition, the proportion of apoptotic IELs after alemtuzumab treatment was significantly higher than in the control group (22.01 ± 3.67 and 6.01 ± 1.42, respectively; P < 0.05). Moreover, the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment.

Conclusions: Alemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model. The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment. Notably, intestinal barrier function may be disrupted after alemtuzumab treatment.

Show MeSH
Related in: MedlinePlus