Double Blockage of TNFα and IL-1β Prevents Islet Graft Damage in Clinical Islet Autotransplantation

B. Naziruddin, M. Takita, F. Kunnathodi, R. Shahbazov, M. Kanak, M. Lawrence, N. Onaca, M. Levy

Islet Cell Laboratory, Baylor Research Institute, Dallas/Fort Worth, TX
Institute of Biomedical Studies, Baylor University, Waco, TX
Baylor Annette C. and Harold C. Simmons Transplant Institute, Dallas, TX

Meeting: 2013 American Transplant Congress

Abstract number: D1581

Background: Total pancreatectomy followed by autologous islet transplantation (TP-AIT) is an advanced surgical option for refractory chronic pancreatitis (CP) patients. Peri-transplant inflammatory reaction can damage islet engraftment.

Methods: A total of 10 CP patients with TP-AIT were analyzed. TNFΑ antagonist (etanercept; 25 mg subcutaneous injection on day 0,1,4 and 7) was given to 5 patients (single blockage: [SB] group). Another 5 patients were administered IL-1Β blocker (anakinra; 100 mg S.C. on day 0 to 7) additionally (double blockage [DB] group). There was no significant difference in pre-transplant basic characteristics (Table). Cytokine profiles were evaluated with Luminex assay system using peri-transplant blood samples.

Table: Pre-transplant basic characteristics
Variables	Single Blockage group (n=5)	Double Blockage group (n=5)	*p value
Age (year)	42±5	45±4	0.36
Sex; Female –n(%)	3 (60%)	3 (60%)	1.0
Body mass index (kg/m²)	24.6±2.5	24.4±1.4	0.95
Disease duration (year)	7±2	10±5	0.62
Fasting C-peptide (ng/mL)	1.6±0.3	1.7±0.4	0.96
Total islet yield (×10³IEQ)	395±164	369±103	0.89
Islet dose (×10³IEQ/kg)	5.7±2.1	5.3±1.4	0.88

Average±S.E. are shown. Student t or Fisher's exact test were employed.

Results: No significant adverse events were observed in both groups. Proinsulin levels in early post-AIT was higher in SB group compared to DB group suggesting islet damage (*p <0.05, Figure). TNFΑ levels were mostly similar between the two groups. DB group had lower IL-1Β levels with significant difference at 1 and 3 hr-post IAT when compared to SB group. Proinflammatory cytokines IP-10 and anti-inflammatory IL-10 levels were inversely regulated between two groups during peri-transplant period.

Conclusions: Double blockage of TNFΑ and IL-1Β offers a safe and better protection for islet grafts from inflammatory reaction during peri-transplant period in autologous islet transplantation.

To cite this abstract in AMA style:

Naziruddin B, Takita M, Kunnathodi F, Shahbazov R, Kanak M, Lawrence M, Onaca N, Levy M. Double Blockage of TNFα and IL-1β Prevents Islet Graft Damage in Clinical Islet Autotransplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/double-blockage-of-tnf-and-il-1-prevents-islet-graft-damage-in-clinical-islet-autotransplantation/. Accessed June 6, 2025.

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