Involvement of CCL18 in inflammatory allergic diseases

The allergic reaction is associated with a local recruitment of Th2 cells, basophils and eosinophils, mainly linked to chemokine production. CCL18 (PARC) is a chemokine preferentially expressed in the lung, secreted by antigen-presenting cells, induced by IL-4, IL-13 and IL-10 and inhibited by IFN-γ. The role of CCL18 was evaluated in the allergic reaction. Peripheral blood mononuclear cells (PBMC) from allergic or non allergic patients were cultured in the presence of the specific allergen. PBMC from house dust mite allergic patients but not from healthy donors secreted CCL18, 48 and 72 hr after Derp 1 stimulation. Among PBMC, plasmocytoid but not myeloid dendritic cells stimulated with Derp 1 for 24 hr secreted CCL18 as well as anti-IgE –stimulated monocytes. Allergen-induced secretion of CCL18 by PBMC was dependent on IL-4 and IL-13 as shown by kinetics of mRNA expression and by inhibition of CCL18 secretion by neutralizing antibodies against these cytokines. Functionally, CCL18 was able to recruit in vitro polarized Th2 lymphocytes and basophils but not eosinophils. To evaluate the in vivo significance of these data, CCL18 was assessed in bronchoalveoalr lavages (BAL) from asthmatic patients and control subjects. CCL18 was increased in BAL from allergic patients as compared to controls. These data suggest that CCL18 may play a role in the allergic reaction.