Oral-Mucosal Administration of IFN-α Potentiates Immune Response in Mice

Abstract

We studied the effects of oral-mucosal administration of murine interferon-alpha (Mu-IFN-alpha) on immune responses and infection with vaccinia virus (VV) in mice. When Mu-IFN-alpha was administered to sheep red blood cell (SRBC)-sensitized mice for 4 or 5 days, Mu-IFN-alpha significantly enhanced delayed-type hypersensitivity (DTH) and antibody production, with maximum enhancement of each at 1 IU/body. To investigate the antiviral effect of oral-mucosal Mu-IFN-alpha, mice were infected with VV, and Mu-IFN-alpha was administered for 15 days. Pocks were observed in the tail skin of infected mice, and Mu-IFN-alpha at doses of 1, 10, and 100 IU/body significantly suppressed pock formation. Also, VV-specific cytotoxic T cells (CTL) were observed in the spleen from the same mice at 7 days after infection, and Mu-IFN-alpha enhanced CTL activity at doses above 1 IU/body. These results suggest that the oral-mucosal Mu-IFN-alpha may have potentiating effects on cellular and humoral immune responses, which may contribute to its effects against VV.

In Vitro Analysis of Virus Particle Subpopulations in Candidate Live-Attenuated Influenza Vaccines Distinguishes Effective from Ineffective Vaccines

“…On the basis of the findings of the present study, the successful vac Because IFN plays a dominant role in successful LAIVs (11,12,13,33), ameliorates pathogenesis (6), and functions as a natural adjuvant (3,4,11,19,41,43), it may be possible to augment the levels of IFN induced endogenously by the vaccine through the exogenous delivery of IFN in drinking water, a procedure used in chickens that allowed the precise control of IFN doses and that is both tactically and economically feasible (19). Peroral use of IFN has also been shown to boost the adaptive immune system in other hosts (26,41,43,46). Low doses of UV radiation enhance even further the IFN-inducing capacity of influenza viruses that express truncated NS1 protein (21) and hence might serve as a second means of augmenting the IFN levels in vaccinated hosts.…”

“…In addition, IFN sensitizes cells to the initiation of apoptosis by viruses (42) and by double-stranded RNA (40), which may be spontaneously released in the course of influenza virus replication (14). Furthermore, IFN functions as an adjuvant to boost the adaptive immune response in mammals (3,4,11,26,41,43,46) and in chickens when administered perorally in the drinking water of influenza virus-infected birds (19). This raises the question: does the enhanced induction of IFN by delNS1 variants suffice to render an infectious influenza virus preparation sufficiently attenuated to function as an effective live vaccine?…”

Efficacy of Low-Dose Oral Use of Type I Interferon in Cytomegalovirus Infections In Vivo

“…Another virus model involved the treatment of C3H/HeN mice with LDOA IFN (1, 10, or 100 IU/mouse) 1 day before vaccinia virus infection and further daily treatment for 15 days p.i. (15) IFNtreated mice in this experimental model showed suppressed pock formation and, at doses greater than 1 IU/mouse, the mice showed enhanced virus-specific cytotoxic T lymphocyte (CTL) activity. Furthermore, antiviral treatment with LDOA human IFN has been reported to be effective between different species.…”

“…(8) The efficacy of LDOA IFN therapy has now been demonstrated in experim ental models (9,10) and clinical settings. (11,12) Several experimental studies including the nonobese diabetes (NOD) mouse model for diabetes, (13) murine B cell tolerance of ovalbumin, (14) vaccinia virus infections in the mouse, (15) and a guinea pig model of asthma (16) have shown the potential for the application of LDOA IFN therapy. In an animal model of MS, LDOA IFN treatment suppressed clinical relapse and adoptive transfer of chronic relapsing experimental autoimmune encephalomyeliti s (CR-EAE).…”

Immune system response to stress factors

“…Interesting inferences can be drawn from the in vitro dose/ response curves of several cytokines which are often bell-shaped. Beyond a narrow concentration range in which the dose response is positive, the response can diminish or even reverse as in the change from stimulation to suppression of the primary antibody response to Sheep Red Blood Cells in interferon-a (IFN-a) treated mice (Nagao et al, 1998). Accordingly, IFN-a abides with the general rule of most cytokines: low dose priming, high dose suppression (Cummins et al, 2005).…”