IL-1R Type 1-Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection.

The IL-1 superfamily of cytokines and receptors has been studied extensively. However, the specific roles of IL-1 elements in host immunity to cutaneous viral infection remain elusive. In this study, we applied vaccinia virus (VACV) by scarification to IL-1R1 knockout mice (IL-1R1-/-) and found that these mice developed markedly larger lesions with higher viral genome copies in skin than did wild-type mice. The phenotype of infected IL-1R1-/- mice was similar to eczema vaccinatum, a severe side effect of VACV vaccination that may develop in humans with atopic dermatitis. Interestingly, the impaired cutaneous response of IL-1R1-/- mice did not reflect a systemic immune deficiency, because immunized IL-1R1-/- mice survived subsequent lethal VACV intranasal challenge, or defects of T cell activation or T cell homing to the site of inoculation. Histologic evaluation revealed that VACV infection and replication after scarification were limited to the epidermal layer of wild-type mice, whereas lack of IL-1R1 permitted extension of VACV infection into dermal layers of the skin. We explored the etiology of this discrepancy and determined that IL-1R1-/- mice contained significantly more macrophages and monocyte-derived dendritic cells in the dermis after VACV scarification. These cells were vulnerable to VACV infection and may augment the transmission of virus to adjacent skin, thus leading to larger skin lesions and satellite lesions in IL-1R1-/- mice. These results suggest new therapeutic strategies for treatment of eczema vaccinatum and inform assessment of risks in patients receiving IL-1 blocking Abs for treatment of chronic inflammatory disorders.

Outcome and clinical significance of delayed endoleaks after endovascular aneurysm repair.

OBJECTIVE: Endovascular aneurysm repair (EVAR) is considered the standard therapy for most patients with abdominal aortic aneurysm (AAA). Endoleak is a well-known EVAR-related complication that requires long-term follow-up. However, patient follow-up is often challenging outside clinical trials. We sought to evaluate the incidence and the effect of delayed endoleaks in a Veterans Administration (VA) health care system where long-term follow-up is ensured. METHODS: We retrospectively evaluated 213 consecutive patients who underwent EVAR at a referral Veterans Administration medical center. Age, aneurysm size, patency of lumbar and inferior mesenteric arteries, and follow-up evaluations were recorded. Type of endoleak, date of detection, and intervention were also documented. Patients who had <1 year of follow-up were excluded. The χ(2) test, Student t-test, Mann-Whitney test, and Spearman correlation were used for data analysis. RESULTS: The analysis included 183 patients with a mean follow-up of 53 months (range, 12-141 months); of these, 48 patients (26%) had endoleaks, and 31 (17%) had aneurysm progression. The mean diagnosis time for nontype II (n = 14) endoleaks was 45 months (range, 3-127 months), and 71% were diagnosed >1 year after EVAR. All except one nontype II endoleak received prompt secondary interventions, and the one without intervention presented with aneurysm rupture. An isolated type II endoleak was detected in 34 patients at an average of 14.4 months (range, 0-76 months) after EVAR, 41% of which were detected >1 year after EVAR. Patients without a documented endoleak had a significant decrease in aneurysm size at the latest computed tomography evaluation compared to the preoperative size (4.8 vs 5.7 cm; P < .001), whereas those with isolated type II endoleak had an increase at the latest computed tomography follow-up compared to preoperative size (5.8 vs 5.7 cm). Importantly, 59% of the patients with a type II endoleak had significant AAA enlargement (0.8 cm), and delayed type II endoleak was significantly associated with sac enlargement compared to type II endoleaks detected early. No significant correlation was seen between the diameter of inferior mesenteric artery or lumbar to AAA enlargement among the patients with a type II endoleak. Secondary interventions in 12 patients with isolated type II endoleak resulted in overall aneurysm stabilization or regression. CONCLUSIONS: This long-term outcome study demonstrated that delayed endoleaks appearing >1 year after EVAR contributed to most of the overall endoleaks and were significantly associated with aneurysm sac growth. This study underscores that type II endoleak is not benign and that vigilant lifelong surveillance after EVAR is critical.