A pig tonsil cell culture model for evaluating oral, low-dose IFN-α treatments

Oral, low-dose IFN-α treatments proved effective in several models of viral infections and immunopathological conditions. Also, they do not give rise to the serious side effects observed after parenteral inoculation of high doses (10(5)U/kg b.w. and higher). There is convincing evidence that such treatments work through an early, effective interaction with oral lymphoid tissues before the IFN-α molecules are rapidly destroyed by gut enzymes. Yet, the paucity of detailed information about these crucial interactions and the lack of recognized in vitro models hamper the development of proper administration protocols. On the basis of a previous study, we developed an in vitro model of interaction between different types of human and porcine IFNs-α at low/moderate concentrations and pig tonsil cells. The IFNs-α under study showed different properties with respect to three fundamental control actions: (1) IgA release in culture, (2) release of natural antimicrobial compounds, and (3) homeostatic regulation of the inflammatory response. This was checked in pig intestinal epithelial cells (IPEC-J2 cell line) treated with supernatants of control and IFN α-treated tonsil cell cultures, respectively, in terms of inflammatory cytokine and chemokine responses. Some IFNs-α caused a significant inhibition of IL-8 (protein release and gene expression) and beta-defensin 1 (gene expression) probably through second messengers released by IFN α-treated tonsil cells. Interestingly, a human lymphoblastoid IFN-α under study caused the decrease of polyclonal IgA release by pig tonsil cells and significantly stimulated the in vitro recall antibody response of swine PBMC to Foot-and-Mouth Disease virus. The modulation of IgA and antibacterial compounds was accompanied by an anti-inflammatory control action at the same, low to moderate IFN-α concentrations (1-100 U/ml). This highlights the very foundation of the homeostatic control actions performed by Type I IFNs: to promote an effective host response to infectious and non-infectious stressors and to turn off noxious inflammatory responses associated with tissue damage and waste of metabolic energy. The described tonsil cell model in vitro can be conducive to a further development of oral cytokine treatments in humans and animals in the "one health" conceptual framework.