Experimental diabetes exacerbates skin transplant rejection in rats

Flávio Pola Dos Reis,Angelo Sementilli,Antonio Ricardo De Toledo Gagliardi

doi:10.1590/s0102-86502013000500001

Flávio Pola Dos Reis, Angelo Sementilli + Show 1 more

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https://doi.org/10.1590/s0102-86502013000500001

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Abstract

To investigate the effect of chronic experimental diabetes on skin allografts in rats as a simple model that could clarify some basic aspects and mechanisms involved in transplant rejection in diabetes compared to normal animals. Skin grafting was performed with fragments of tail skin from sex matched non diabetic Wistar rats engrafted onto the thoracic area of diabetic and non diabetic recipients. Grafts were scored for rejection every other day and were removed on day 14. Skin grafts were graded according to the following itens: no rejection; or rejection including: acute, chronic and humoral and/or cellular rejection. Statistical analysis was performed using JMP 5.1 software with ANOVA test. Diabetes was induced with IV injection of alloxan 40 mg/kg. Inflammatory vascular infiltrate compromising the endothelium with areas of fibrinoid necrosis and thrombosis characteristics of acute humoral rejection and subendothelial lymphocyte infiltrate typical of acute cellular rejection were significantly (p<0.003) higher in diabetic than in non diabetic recipients as the inflammatory infiltrate in the epidermis (p<0.002). Skin transplant acute rejection from chronic alloxan diabetic rats to normal tissue was significantly more intense than the acute rejection between normal rats.

Highlights

Diabetes mellitus (DM) is an important cause of mortality and morbidity worldwide, through both direct clinical complications and the high risk for cardiovascular and kidney diseases
We investigated the effect of chronic experimental diabetes on skin allografts in rats as a simple model that could clarify some basic aspects and mechanisms involved in acute transplant rejection in diabetes
Dermal inflammatory infiltrate in G1 was mix with 40% lymphocytic and 60% mononuclear

Summary

Introduction

Diabetes mellitus (DM) is an important cause of mortality and morbidity worldwide, through both direct clinical complications and the high risk for cardiovascular and kidney diseases. The proportion of patients with diabetes mellitus that progresses to End Stage Renal Disease is increasing. The increased prevalence of diabetes mellitus is estimated to account for 28% incidence of renal replacement therapy in general[2] and diabetes mellitus is the most common cause of end-stage renal disease in the United States, accounting for up to 46% of patients on renal replacement therapy each year[3]. The prevalence of rejection in patients with diabetes mellitus is slightly but not significantly higher than in non-diabetic subjects[4]. It has been shown that the five year graft survival was 74% for nondiabetics, 72% for those with type 1 diabetes and 47% for those with type 2 diabetes. Ten year graft survival was 65% for non-diabetics and 59% for those with type 1 diabetes. Forty-four percent of the non-diabetic recipients developed acute rejection episodes, as did 50% of recipients with type 1 and 57.1% of recipients with type 2 diabetes[5]

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