International Journal of Immunopharmacology
The anti-allergic drug histaglobin inhibits NF-κB nuclear translocation and down-regulates proinflammatory cytokines
Introduction
The anti-allergic drug histaglobin is used to treat allergic diseases such as bronchial asthma, allergic rhinitis and atopic dermatitis [1], [2], [3]. The drug was developed on the basis of the concept of histamine fixation to human serum [4]. Histaglobin has been reported to inhibit antigen-induced histamine release from human peripheral blood basophils and from rat peritoneal mast cells [5], [6], [7]. In addition, histaglobin has been shown to inhibit the allergen-induced peritoneal accumulation of eosinophils at inflammation sites [8]. The precise mechanism underlying the anti-allergic functions of histaglobin has yet to be investigated. In view of the important role that inflammatory cytokines and mediators play in regulating different types of allergy and asthma, we investigated the effect of histaglobin on IL-1β, TNF-α, IL-6 and IL-10 release from human peripheral blood mononuclear cell cultures. We also focused on the role of the transcription factor NF-κB because of its central involvement in mediating a wide variety of target genes that participate in inflammatory processes.
Section snippets
Reagents
Histaglobin was provided by Biobasal AG, Basel, Switzerland. The synthetic lipopeptide used in this study, N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(R,S)-propyl]-(R)-cysteinyl-seryl-(lysyl)3-lysine (P3CSK4), was obtained from ECHAZ microcollections, Tübingen, Germany. LPS from Salmonella abortus equi was kindly provided by C. Galanos (Max-Planck Institut für Immunbiologie, Freiburg, Germany). Recombinant mouse TNF-α was purchased from Pharmingen-Europe, Hamburg, Germany. Phytohemagglutinin (PHA)
Histaglobin inhibits the release of IL-1β, TNF-α, IL-6 and IL-10 from human peripheral blood mononuclear cells
The effect of histaglobin on IL-1β release was investigated using PBMCs. Treatment with histaglobin (75 and 300 μg/ml) for 72 h resulted in a marked reduction (p<0.001) of the constitutive IL-1β release into the medium in a dose-dependent manner (Fig. 1). Histaglobin also significantly (P<0.001) reduced the release of IL-1β from PBMCs activated with the T-lymphocyte mitogen PHA to the level of control cells treated with histaglobin alone.
In order to further characterize the inhibitory effect of
Discussion
In our study we looked for cellular targets involved in inflammatory reactions that could be potentially regulated by the anti-allergic drug histaglobin. We found that histaglobin down-regulates the release of the proinflammatory cytokines IL-1β and TNF-α from blood leukocytes (PBMC). These cytokines play a substantial role in the regulation of inflammatory responses: IL-1β and/or TNF-α have been shown to correlate with the induction of inflammatory mediators in smooth muscle cells, endometrial
Acknowledgements
We gratefully appreciate the excellent technical assistance of B. Erhard, B. Treyer and K. Vukovic. We thank Dr. K. Nübler-Jung for the critical review of this publication.
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