Travis L. Holloway

The association between the Th-17 immune response and pulmonary complications in a trauma ICU population.

BACKGROUND The overall immunopathology of the T-helper cell (Th)-17 immune response has been implicated in various inflammatory diseases including pulmonary inflammation; however its potential role in acute respiratory distress syndrome (ARDS) is not defined. This study aimed to evaluate the Th-17 response in bronchoalveolar lavage fluid (BALF) and blood and from trauma patients with pulmonary complications. METHODS A total of 21 severely injured intensive care unit (ICU) subjects, who were mechanically ventilated and undergoing bronchoscopy, were enrolled. BALF and blood were collected and analyzed for Th-1 (interferon [IFN]γ), Th-2 (interleukin [IL]-4, -10), Th-17 (IL-17A, -17F, -22, 23) and pro-inflammatory (IL-1β, IL-6, tumor necrosis factor [TNF]α) cytokine levels. RESULTS Significant levels of the Th-17 cytokines IL-17A, -17F and -21 and IL-6 (which can be classified as a Th-17 cytokine) were observed in the BALF of all subjects. There were no significant differences in Th-17 cytokines between those subjects with ARDS and those without, with the exception of plasma and BALF IL-6, which was markedly greater in ARDS subjects, as compared with controls and non-ARDS subjects. CONCLUSIONS Trauma patients with pulmonary complications exhibited a significant Th-17 response in the lung and blood, suggesting that this pro-inflammatory milieu may be a contributing factor to such complications.

Tumorous PASH presenting as rapid unilateral breast enlargement.

36-year-old woman presented with a 3-month history of progressive, rapid enlargement of the right breast. She had no family history of breast diseases and had not been taking any medications. On examination, the right breast was dramatically enlarged when compared with the left (Figure 1). We obtained a bilateral diagnostic mammogram, ultrasonography, core biopsies (Figure 2 ,A ), and magnetic resonance imaging (Figure 2 ,B ) of the right breast. Pathologic examination revealed pseudoangiomatous stromal hyperplasia (PASH), with no evidence of malignancy. The patient underwent a bilateral mastectomy with immediate breast reconstruction, and the tumor resected from the right breast measured 11.0 8.5 6.0 cm and weighed 666.0 g. The final pathologic findings were consistentwithtumorousPASH. 1 Thisisamong thelargestPASHtumorsreportedinthemedical literature. The patient had an excellent clinical and cosmetic outcome. An incidental finding of microscopic PASH

Dermal γδ T-cells can be activated by mitochondrial damage-associated molecular patterns

Background Gamma delta T-cells have been shown to be important to the early immunoinflammatory response to injury, independent of infection. This unique T-cell population acts to regulate cell trafficking and the release of cytokines and growth factors. We propose this sterile inflammatory response is in part associated with damage associated molecular patterns (DAMPs) generated by major injury, such as burn, and mediated via toll-like receptors (TLRs). It is unknown whether DAMPs can activate resident γδ T-cells that reside in skin. Methods Gamma delta T-cells were isolated from the skin of male C57BL/6 mice by enzymatic digestion. Mitochondrial DAMPs (MTDs) were generated from mitochondria isolated from mouse livers by sonication and centrifugation. Dermal γδ T-cells were incubated with MTDs (0–500 μg/ml) for 24 hr and cells and supernatants were collected for analysis. Results MTDs activated dermal γδ T-cells, as evidenced by increased TLR2 and TLR4 expression following in vitro exposure. MTDs also induced the production of inflammatory cytokines (IL-1β, IL-6), and growth factors (PDGF and VEGF) by γδ T-cells. Conclusions These findings herein support the concept that MTDs released after tissue/cellular injury are capable of activating dermal γδ T-cells. We propose that the activation of this unique T-cell population is central in the initiation of sterile inflammation and also contributes to the subsequent healing processes.