Changes in plasma IL-1beta, TNF-alpha and IL-6 after total hip replacement surgery in general or regional anaesthesia.

Different anaesthetic methods influence the neuro-immuno-endocrine biologic responses to surgery and may thus possibly interfere with the postoperative course and development of complications. The neuroendocrine system is closely related to the cytokine network. In this study, the effects of general anaesthesia (n=6) and regional spinal/epidural anaesthesia (n=6) on the cytokine response (IL-1beta, TNFalpha, IL-6) to uncemented total hip replacement surgery were evaluated. The postoperative clinical course was uneventful in every case. In both groups, only very low values of plasma IL-beta were measured perioperatively, whereas plasma IL-6 increased postoperatively with peak values 4 h after surgery. The changes in plasma TNF-alpha were not significant. No significant differences in plasma TNF-alpha or IL-6 were found between patients operated in general or in regional anaesthesia. This suggests minor influence of plasma cytokines on the possible beneficial effects of regional anaesthesia on the clinical course after surgery in low risk patients. There were slightly higher TNF-alpha and IL-6 levels after the operation and significantly lower cortisol levels during the operation in the regional anaesthesia group compared to the general anaesthesia group, giving rise to a significant inverse correlation between peak values of IL-6 and peak values of cortisol. This supports the theory that after surgery the inhibitory effect of cortisol on monocyte cytokine production overrides adrenergic stimulation.

Reactivity of T cells with grass pollen allergen extract and allergoid.

BACKGROUND: Successful allergen-specific immunotherapy is achieved with progressively increasing doses of allergen or allergoid. In order to gain further insight into the mechanism of action of allergoids several in vitro investigations were conducted. METHODS: Peripheral blood mononuclear cells (PBMC) from grass pollen allergic and nonallergic subjects were stimulated with either grass pollen extract or allergoid and the proliferation and cytokine production (IL-5, IFN-gamma) were measured. Similar investigations were performed with Phl p 5-specific T cell lines (TCL) and clones (TCC). Dendritic cells and PBMC were compared in terms of their relative efficacies as antigen-presenting cells. RESULTS: Both allergen and allergoid induced proliferation and Th2 and Th1 cytokine synthesis by PBMC of allergic subjects, whereas PBMC of nonallergic subjects did not produce IL-5. The maximum level of IL-5 was obtained with a lower concentration than was necessary for maximal IFN-gamma production. Higher stimulation doses of allergen and allergoid shifted the cytokine profiles towards a Th1 phenotype. TCL and TCC clearly showed reactivity with both allergen and allergoid when using autologous PBMC for antigen presentation, but compared with the native allergen the reactivity of the allergoid was reduced with most of the TCC. Using dendritic cells for antigen presentation a pronounced increase of stimulation of the TCC especially for the allergoids becomes obvious. CONCLUSION: In common with grass pollen allergen the corresponding allergoids possess a strong allergen-specific T cell-stimulating capacity. However, the degree of T cell stimulation by the allergoid seems to be dependent on the type of the antigen-presenting cell. Both, allergen and allergoid, can modulate T cell responses in a dose-dependent manner.

Allergen-stimulated expression of CD154 (CD40 ligand) on CD3+ lymphocytes in atopic, but not in nonatopic individuals. Modulation by bacterial lipopolysaccharide.

The intention of this study was to mimic a naturally occurring stimulation by allergens and bacterial infection in order to determine whether specific allergen-induced, inflammatory responses may be changed or modified by bacterial products. Blood leukocytes from six atopic and six nonatopic individuals were examined for their surface expression of CD154, CD11a, and HLA-DR molecules and for secretion of IgE, eosinophil cationic protein (ECP), and the cytokines interleukin (IL)-4 and IL-5. Signals through CD154 are required for activation and proliferation of effector cells associated with the allergic, inflammatory response. HLA-DR and CD11a/CD18-mediated interactions are also involved in T- and B-cell functions. Birch-pollen (BP) allergens induced CD154 expression on CD3-positive lymphocytes only in atopic individuals. In nonatopics, the expression of CD154 could be induced only after exposure to BP and subsequent lipopolysaccharide (LPS) stimulation. Levels of CD154 expression were always higher in atopics than nonatopics. CD11a and HLA-DR expressions were upregulated, irrespective of atopic state, after BP and/or LPS stimulation. The increased secretion of IL-5 and total IgE in BP-supplemented cell cultures indicated that an allergic response had occurred. In conclusion, the results of this report do not support the hypothesis of a changed inflammatory response stimulated by the combined action of bacteria and allergens, as compared to allergen provocation alone.