We examined the effects of beta2-adrenergic receptor (beta2-AR) agonists on the expression of co-stimulatory molecules on lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells. The study found that beta2-AR agonists inhibited the expression of intercellular adhesion molecule-1 (ICAM-1), CD40 and CD14 on monocytes, and that AR agonist activity was antagonized by the selective beta2-AR antagonist, butoxamine. The selective beta2-AR agonists salbutamol and terbutaline induced a similar co-stimulatory molecule expression pattern. The LPS-induced production of tumour necrosis factor-alpha was inhibited by AR agonists, and this was also antagonized by butoxamine, and mimicked by salbutamol and terbutaline. The AR agonists also inhibited T-cell proliferation through beta2-AR stimulation. This study clearly demonstrated that endogenous catecholamines elicited immunosuppressive effects through beta2-AR stimulation, possibly due to down-regulation of the expression of ICAM-1, CD40 and CD14 on monocytes. These results suggested that the sympathetic nervous system might regulate the T-helper cell balance via the peripheral end-effectors of the stress system.

Interleukin (IL) 18, a powerful inducer of the immunoregulatory cytokine interferon-gamma (IFN-gamma), presents upstream of the cytokine activation cascade in the inflammatory response. The anti-inflammatory properties of steroids permit their use in various conditions, although effects are transient and pathological states are not fully relieved by short-term steroidal use. We examined the effect of lipopolysaccharide (LPS)/IL-2 on the cytokine cascade in human peripheral blood mononuclear cells (PBMCs). We also examined the effect of steroids on LPS/IL-2-induced cytokine production in human PBMCs taken from healthy volunteers. Cell-free supernatant fractions were assayed for IL-18, IL-12, IL-2, IFN-gamma and IL-10 protein, using enzyme-linked immunosorbent assays, and synergy between LPS and IL-2 in enhanced production of IL-18 was observed. Steroids suppressed the production of IL-18 and other secondary cytokines in LPS/IL-2-stimulated PBMCs, in a concentration- and time-dependent manner, although inhibition was incomplete even at high concentrations. Effects of steroid treatment on expression of membrane-bound LPS receptor antigen (mCD14) and intercellular adhesion molecule-1 (ICAM-1) in PBMCs were studied by flow cytometric analysis. Steroid treatment up-regulated mCD14 expression in a concentration-dependent manner, with no effect on ICAM-1 expression. These results suggest that the incomplete counteraction of steroids in the LPS/IL-2-initiating cytokine cascade is due, at least partly, to the up-regulation of mCD14 by steroid preparations, which increases susceptibility to bacterial endotoxins.

Surface antigens on peripheral blood eosinophils from 23 patients with bronchial asthma, 6 with eosinophilic pneumonia and 8 controls were examined using a new direct method. Peripheral blood eosinophils in bronchial asthma and eosinophilic pneumonia showed higher complexity and/or granularity than those from controls. The percentage expression of HLA DR, CD4 and CD45RO on peripheral blood eosinophils from patients with bronchial asthma were increased compared with those from patients with eosinophilic pneumonia and from the controls. These results suggest that peripheral blood eosinophils in bronchial asthma may play a role in immunoregulation via the expression of human leukocyte antigens, such as HLA-DR, CD4 and CD45RO, that interact with lymphocytes, and may function as antigen-presenting cells. Furthermore this study suggests that there may be different phenotypes of eosinophils with differing surface antigens and intercellular reactions between eosinophils and lymphocytes.

Bronchoalveolar lavage was performed in patients with chronic eosinophilic pneumonia of unknown origin diagnosed histopathologically, and the alveolar fluid cells were investigated before and during corticosteroid therapy. The counts of eosinophils in bronchoalveolar lavage fluid decreased markedly during steroid therapy compared with before therapy, and the ratios of interleukin 2 receptor-positive T cells and HLA DR-positive T cells to all T lymphocytes in the lavage fluid also decreased. Both before and during steroid therapy, many macrophages in bronchoalveolar lavage fluid phagocytosed EG2-positive granules and stained immunohistochemically as CD71-positive ‘responsive macrophages’. The decrease of activated T lymphocytes and the active phagocytosis of eosinophil granules by macrophages might play an important role in the mechanism of healing in chronic eosinophilic pneumonia.

No abstract