The article by Kiss et al. [1] on interferon-alpha (IFNa) therapy in children with malignancies and Langerhans cell histiocytosis (LCH) serves to remind us of the growing body of evidence that speaks to the efficacy of this cytokine in the treatment of . Moreover, it gives us the opportunity of considering what molecular pathways may be present and vulnerable to this approach in the LCH-histiocyte.
IFNa both downregulates protein kinase C (PKC)alpha (a) expression while exerting antiproliferative effects [10] and takes advantage of the presence of PKC pathways to produce growth inhibitor/cytolytic effects [11][12][13]. We therefore applied immunohistochemical probes for the detection of the total and the phosphorylated forms of PKC-a and PKC-beta (b) II in archival material from seven patients with osteolytic LCH. Cytoplasmic and/or plasmalemmal expression of PKC-a antigen was evident in all seven cases (Fig. 1). In contrast, immunoreactivity for PKC-bII was either absent or mild (Fig. 1). Concurrent plasmalemmal and/or cytoplasmic localization of the phosphorylated form of PKC-a/bII antigen was also noted in all biopsy specimens (Fig. 1).
The expression and apparent activation (phosphorylation) of PKC-a accord with the presence of interleukin (IL)-1a (which we also demonstrated in all of these LCH