pulmicort and Encephalitis

Chronic asthma is one of the most common respiratory diseases, characterized by airway inflammation. However, little is known whether asthma-induced airway inflammation might influence the brain. We found that chronic asthma not only resulted in peripheral inflammation, but also induced neuroinflammation which was characterized by microglial activations and increased levels of TNFα and IL-1β in the hippocampus and prefrontal cortex. Simultaneously, we found that there was significant neuronal loss in the asthmatic mouse brain. Inhaled budesonide, the classic therapeutic drug for chronic asthma, could inhibit asthma-induced microglial activation, down-regulate TNFα and IL-1β but up-regulate TGFβ and IL-10 of mouse brain, and thereby attenuate neuronal loss. Further study showed that chronic asthma increased the expressions of TLR4 and p65/NFκB in the brain, which could be reversed by budesonide treatment. Therefore, the present study reveals that inhaled budesonide protects against asthma-induced neuroinflammation in mouse brain, which might be contributed to attenuate neuronal loss.

Topics: Administration, Inhalation; Analysis of Variance; Animals; Anti-Inflammatory Agents; Asthma; Brain; Bronchoalveolar Lavage Fluid; Budesonide; CD11b Antigen; Cytokines; Disease Models, Animal; Encephalitis; Female; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; Signal Transduction; Toll-Like Receptor 4

Platelet activating factor (PAF; beta-acetyl-gamma-O-hexadecyl-l-alpha-phosphatidylcholine) triggers a rapid pro-inflammatory gene expression program in primary cultures of human neural (HN) cells. Two genes and gene products consistently induced after PAF treatment are the cytosoluble prostaglandin synthase cycloooxygenase-2 (COX-2) and the pro-apoptotic tumor necrosis factor alpha (TNFalpha). Both of these mediators are associated with the activation of inflammatory signaling, neural cell dysfunction, apoptosis and brain cell death, and both have been found to be up-regulated after brain injury in vivo. In this study we investigated the effects of the non-halogenated synthetic glucocorticoid budesonide epimer R (BUDeR), the novel PAF antagonist LAU-0901, and the electron spin trap and free radical scavenger phenyl butyl nitrone (PBN), upon early COX-2 and TNFalpha gene activation and prostaglandin E(2) (PGE(2)) release in PAF-stressed primary HN cells. The data indicate that these three biochemically unrelated classes of inflammatory repressors act synergistically in modulating PAF-induced up-regulation of COX-2, TNFalpha, and PGE(2) by quenching oxidative stress or inflammatory signaling, resulting in increased HN cell survival. These, or analogous classes of compounds, may be useful in the design of more effective combinatorial pharmacotherapeutic strategies in the treatment of complex neuro-inflammatory disorders.

Topics: Anti-Inflammatory Agents; Budesonide; Cell Survival; Cells, Cultured; Cyclic N-Oxides; Cyclooxygenase 2; Dihydropyridines; Dinoprostone; Drug Synergism; Encephalitis; Gene Expression; Humans; Neurons; Oxidative Stress; Platelet Activating Factor; Signal Transduction; Stress, Physiological; Transcriptional Activation; Tumor Necrosis Factor-alpha; Up-Regulation