Nlrp1 inflammasome is downregulated in trauma patients.

UNLABELLED: After a major trauma, IL-1ß-producing capacity of monocytes is reduced. Generation of IL-1ß is important for appropriate immune response after trauma and requires not only synthesis and transcription of inflammasome components but also their activation. Altered IL-1ß-processing due to deregulated NLRP inflammasomes assembly is associated with several inflammatory diseases. However, the precise role of NLRP1 inflammasome in monocytes after trauma is unknown. Here, we investigated if NLRP1 inflammasome components are responsible for depressed monocyte function after trauma. We found in ex vivo in vitro assays that LPS-stimulation of CD14(+)-isolated monocytes from healthy volunteers (HV) results in remarkably higher capacity of the IL-1ß-release compared to trauma patients (TP). During the 10-day time course, this monocyte depression was highest immediately after admission. Inflammasome activation correlating with this inflammatory response was demonstrated by enhanced protein production of cleaved IL-1ß and caspase-1. Furthermore, we found that the gene expression of IL-1ß, caspase-1, and ASC was comparable in TP and HV after LPS-stimulation during the 10-day course, while NLRP1 was markedly reduced in TP. We demonstrated that transfected monocytes from TP, which expressed the lacking components, were recovered in their LPS-induced IL-1ß-release and that lacking of NLRP1 is responsible for the suppressed monocyte activity after trauma. The restoration of NLRP1 inflammasome suggests new mechanistic target for the recovery of dysbalanced immune reaction after trauma. KEY MESSAGE: Suppression in monocyte function occurs early after a major trauma or surgery. Reduced gene expression abrogates NLRP1 inflammasome assembly after trauma. Limited availability of inflammasome components may cause reduced host defense. Restoring NLRP1 in immune-suppressed monocytes recovers NLPR1 activity after trauma. Recovered inflammasome activity may improve the immune response to PAMPs/DAMPs.

Activation of nevi in patients with malignant melanoma.

Activation of melanocytic nevi from patients with malignant melanoma is documented microscopically. Features of activation include marked junctional activity, lack of lateral margination of junctional melanocytic activity, and--to a lesser degree--increased pigment production, inflammation, mitotic activity, and cytologic atypia. The changes are most pronounced in nevi from the same lymph drainage region as the malignant melanoma, suggesting a local activating factor. The presence of marked junctional activity in these lesions and the occurrence of these changes in nevi of patients with clinical Stage I malignant melanomas provide evidence that these lesions do not represent metastases.

Spontaneous regression of pulmonary leiomyomas during pregnancy.

Multiple pulmonary nodular densities simulating metastastic cancer were discovered in a routine chest roentgenogram of a 30-year-old pregnant woman. Lung biopsy revealed nodules composed of smooth muscle and collagenous tissue containing entrapped glandular elements. The lesions were initially interpreted as multiple pulmonary fibroleiomyomatous hamartomas (MPFLH). During pregnancy and the post-partum period, the pulmonary nodules regressed spontaneously. Critical analysis of the published cases as well as our own case indicates that multiple pulmonary fibroleiomyomatous hamartomas (MPFLH) cannot be distinguished from benign metastasizing leiomyoma (BML) by either clinical, roentgenographic, or pathologic criteria and that all represent pulmonary metastases from a primary uterine neoplasm. The spontaneous regression of the pulmonary nodules in the present case as well as the increased risk for development of progressive pulmonary insufficiency in the pre-menopausal patients indicates an apparent hormonal dependence. Total abdominal hysterectomy and bilateral salpingo-oophorectomy appears to be the treatment of choice.