Proinflammatory and Th2-derived cytokines modulate CD40-mediated expression of inflammatory mediators in airway epithelia: implications for the role of epithelial CD40 in airway inflammation.

Cytokines produced by activated macrophages and Th2 cells within the lung play a key role in asthma-associated airway inflammation. Additionally, recent studies suggest that the molecule CD40 modulates lung immune responses. Because airway epithelial cells can act as immune effector cells through the expression of inflammatory mediators, the epithelium is now considered important in the generation of asthma-associated inflammation. Therefore, the goal of the present study was to examine the effects of proinflammatory and Th2-derived cytokines on the function of CD40 in airway epithelia. The results show that airway epithelial cells express CD40 and that engagement of epithelial CD40 induces a significant increase in expression of the chemokines RANTES, monocyte chemoattractant protein (MCP-1), and IL-8 and the adhesion molecule ICAM-1. Cross-linking epithelial CD40 had no effect on expression of the adhesion molecule VCAM-1. The proinflammatory cytokines TNF-alpha and IL-1beta and the Th2-derived cytokines IL-4 and IL-13 modulated the positive effects of CD40 engagement on inflammatory mediator expression in airway epithelial cells. Importantly, CD40 ligation enhanced the sensitivity of airway epithelial cells to the effects of TNF-alpha and/or IL-1beta on expression of RANTES, MCP-1, IL-8, and VCAM-1. In contrast, neither IL-4 nor IL-13 modified the effects of CD40 engagement on the expression of RANTES, MCP-1, IL-8, or VCAM-1; however, both IL-4 and IL-13 attenuated the effects of CD40 cross-linking on ICAM-1 expression. Together, these findings suggest that interactions between CD40-responsive airway epithelial cells and CD40 ligand+ leukocytes, such as activated T cells, eosinophils, and mast cells, modulate asthma-associated airway inflammation.

Recovery of alveolar macrophages from rhesus and cynomolgus macaques by lung lavage.

A lung lavage technique was developed to recover alveolar macrophages from rhesus and cynomolgus macaques. Sterile saline solution was injected through an endotracheal tube in anesthetized macaques; lung wash fluids containing leukocytes were withdrawn. The lung wash fluids from each animal routinely contained more than 16 x 10(6) leukocytes. The predominant cell type was the alveolar macrophage; lung wash fluids contained more than 53% and 80% alveolar macrophages from rhesus and cynomolgus macaques, respectively. Lung lavage was performed each week for 6 weeks in both species with no ill effects. This technique has many applications in the study of infection and of pulmonary defense mechanisms.

The phenomenon of tobacco smoking.

The social acceptance of tobacco prevents recognition of the fact that most regular smokers are addicted to nicotine. We have no facilities for dealing with this problem and there are no specific treatments; but group techniques may help some smokers to quit. Education and research may eventually provide solutions; but to date they have not been effective. Realistic expectations and acceptance of his limitations will permit the family physician to save time and energy when he is confronted by a persistent smoker.

Hyperkinesis and maternal smoking.

Mothers of methylphenidate-sensitive hyperkinetic children reported smoking two to three times as many cigarettes as the mothers of dyslexic and normal controls; the reported cigarette consumptions of the fathers showed no significant differences. These findings are consistent with the hypothesis that smoking during pregnancy is an important cause of the hyperkinetic syndrome.

Complications of therapy with lysergide.

All known complications which occurred during and after LSD treatment of 237 psychiatric patients on an open ward of a general hospital are described and classified. The results imply that clinical research with lysergide can be carried out in similar settings with relative safety.