Cytokines in sensitization to aeroallergens

Abstract

Knowledge about the immunological mechanisms underlying asthma bronchiale is a prerequisite for development of new (causal) interventions. A large number of studies has proven asthma to be a complex disease with subtypes with different immunological features. Cytokines and chemokines, which are secreted by immune cells as well as structural cells play an important role not only in maintenance and amplification but have significant impact in the initiation of pulmonary inflammations - the asymptomatic sensitization phase. This article describes important immunological mediators in the context of the pulmonary sensitization phase. Moreover chances and constraints of intervention strategies aiming at these mediators are discussed. Several new aspects like classification of immunological phenotypes in bronchial asthma for individualized strategies and taking the sensitization phase into account, reveal possible targets among both "old acquaintances" like IL-4 and newly identified mediators (e.g. IL-17, IL-33).

Keywords: asthma; cytokines; sensitization.

Figure 1.. Sensitization phase and effector phase in allergic bronchial asthma. Th = T helper cell; DC = dendritic cell.

Figure 2.. Schematic presentation of the cytokine network during pulmonary sensitization. For explanation, see text. Baso = basophil granulocyte; Th = T helper cell; DC = dendritic cell; AAM = alternatively activated macrophage; TSLP = thymic stromal lymphopoeitin; GM-CSF = granulocyte-macrophage-colony-stimulating factor; TNF = tumor necrosis factor; TCR = T cell receptor; MHCII = major histocompatibility complex II.

Figure 3.. IL-17-producing Th17 cells mediate pulmonary new sensitization. After transferring ovalbumin-specific Th17 cells into naïve animals, the acute Th17-polarized airway inflammation is triggered by intra-nasal challenge (1^st challenge) with ovalbumin (O). When an unknown antigen (K) is simultaneously administered intra-nasally, new sensitization against this antigen occurs. This new sensitization is then confirmed in a 2^nd challenge phase by single administration of the previously unknown antigen (K) as compared to a positive control with the known antigen ovalbumin (O) (control animals do not receive cell transfer: nil): A: Airway inflammation: number and differentiation of cells in the bronchoalveolar lavage fluid (BAL). B: Systemic sensitization: KLH-specific antibody concentration in the serum. C: Airway hyperresponsiveness: effective methacholine dose (ED) necessary to achieve an increase in lung resistance (RL) by 150%.