Initiation of LPS-induced pulmonary dysfunction and its recovery occur independent of T cells

Abstract

BackgroundThe acute respiratory distress syndrome (ARDS) is a serious disease in critically ill patients that is characterized by pulmonary dysfunctions, hypoxemia and significant mortality. Patients with immunodeficiency (e.g. SCID with T and B cell deficiency) are particularly susceptible to the development of severe ARDS. However, the role of T cells on pulmonary dysfunctions in immune-competent patients with ARDS is only incompletely understood.MethodsWild-type (wt) and RAG2−/− mice (lymphocyte deficient) received intratracheal instillations of LPS (4 mg/kg) or saline. On day 1, 4 and 10 lung mechanics and bronchial hyperresponsiveness towards acetylcholine were measured with the flexiVent ventilation set-up. The bronchoalveolar lavage fluid (BALF) was examined for leukocytes (FACS analysis) and pro-inflammatory cytokines (ELISA).ResultsIn wt mice, lung mechanics, body weight and body temperature deteriorated in the LPS-group during the early phase (up to d4); these alterations were accompanied by increased leukocyte numbers and inflammatory cytokine levels in the BALF. During the late phase (day 10), both lung mechanics and the cell/cytokine homeostasis recovered in LPS-treated wt mice. RAG2−/− mice experienced changes in body weight, lung mechanics, BAL neutrophil numbers, BAL inflammatory cytokines levels that were comparable to wt mice.ConclusionFollowing LPS instillation, lung mechanics deteriorate within the first 4 days and recover towards day 10. This response is not altered by the lack of T lymphocytes suggesting that T cells play only a minor role for the initiation, propagation or recovery of LPS-induced lung dysfunctions or function of T lymphocytes can be compensated by other immune cells, such as alveolar macrophages.Electronic supplementary materialThe online version of this article (10.1186/s12890-018-0741-2) contains supplementary material, which is available to authorized users.

Insights into pathogenesis of fatal COVID‐19 pneumonia from histopathology with immunohistochemical and viral RNA studies

“…However, in DAD due to other aetiologies, neutrophils have been described early in the course of disease and other chronic inflammatory cells in later stages regardless of whether mechanical ventilation has been used or not. 21,[34][35][36][37][38][39] In other viral pneumonias, including influenza [40][41][42][43] and Ebola, 44 the host inflammatory response has been shown to play a distinct role in pathogenesis in addition to direct damage from viral infections. It is reasonable to hypothesise that this is also the case in severe SARS-CoV-2 infections, but more research on this question is needed.…”

“…We cannot exclude the possibility that the presence of these chronic inflammatory cells could be related to the longer periods of mechanical ventilation in these patients. However, in DAD due to other aetiologies, neutrophils have been described early in the course of disease and other chronic inflammatory cells in later stages regardless of whether mechanical ventilation has been used or not 21,34–39 . In other viral pneumonias, including influenza 40–43 and Ebola, 44 the host inflammatory response has been shown to play a distinct role in pathogenesis in addition to direct damage from viral infections.…”

MCTR1 alleviates lipopolysaccharide‐induced acute lung injury by protecting lung endothelial glycocalyx

“…However, 3 hr after LPS exposure, Mch (10-300 mg/ml) challenge induced significantly higher increases in lung resistance than PBS exposure alone. By 6 and 24 hr post-LPS exposure, these effects on lung function returned to near baseline levels, and no significant differences relative to the PBS controls were apparent (Verjans et al, 2018). In this study, we demonstrated that compared with the control treatment, MCTR1 treatment improves the survival rate of septic mice.…”

Bronco T (Shirisadi kasaya), a polyherbal formulation ameliorates LPS induced septicemia in rats

“…In the 2nd phase, the host's immune response is partially deregulated, resulting in an imbalance between pro-inflammatory and anti-inflammatory cytokine responses that ultimately leads to life-threatening tissue damage, multiple organ failure, and vascular dysfunction and death. Sepsis is frequently associated with ARDS characterized by severe respiratory failure with reduced pulmonary functioning and increased oxidative stress (5). As sepsis progresses the heart starts beating rapidly and breathing becomes rapid as a compensatory mechanism in the initial stage but followed by a drop in blood pressure (6), resulting from reduced oxygen supply to vital organs like the brain, heart, lungs and kidney leading to multiple organ failure (7).…”