The present report provides evidence to support the hypothesis that peptides released during an immune response alter CNS activity and thus may provide a means for the immune system to transmit afferent signals into the brain. Specifically, it is demonstrated that recombinant interferon-alpha (rIFN-alpha), a peptide associated with the immune response to viral infection, can alter opiate withdrawal severity in a dose-dependent manner upon direct injection into brain areas essential for this phenomenon. These results are compared and contrasted with the effect of systemically injected rIFN-alpha upon opiate withdrawal. In addition, an electrophysiological investigation into the basis of the interaction of opioids and rIFN-alpha in brain structures essential for the expression of opioid activities is also presented. Finally, the effects of rIFN-alpha upon the functions of both the CNS and other systems is discussed in terms of the effects reported for other peptides associated with immune responses.

Defective gut immune reactions have been implicated in the development of atopic dermatitis (AD), whereas oral tolerance (OT), that is, the immune unresponsiveness induced by oral antigen administration, protects mice against AD. To investigate this protective role of OT, the transcriptomic profiles of skin were obtained by RNA sequencing from mice that were epicutaneously sensitized, orally tolerized prior to epicutaneous sensitization, or neither (control). Oral tolerance inhibited the upregulation of keratin- and allergic inflammation-associated genes that occurred in the epicutaneously sensitized group. Compared to the controls, mice that were orally tolerized and epicutaneously sensitized showed an upregulation of genes that regulate inflammation or keratinocyte differentiation. Knocking down two of those genes, SCGB1A1 and TSC22D3, upregulated Th2 inflammatory mediators and downregulated a cornified cell envelope-related gene. Based on our findings, OT may protect skin against allergic inflammation by promoting the expression of genes that regulate Th2 inflammatory responses and skin barrier function.