Inhibition by interferon of delayed-type hypersensitivity in the mouse.

Abstract

The effect of interferon on delayed-type hypersensitivity to picryl chloride and sheep erythrocytes was examined in the mouse. When administered to sensitized animals on the day .before or the day of challenge, tissue culture interferon inhibited both the ear swelling induced by picryl chloride and footpad swelling induced by sheep erythrocytes. Newcastle disease virus, when injected into sensitized If-11 or If-14 congenic mice a few hours before challenge, caused an inhibition of delayedtype hypersensitivity which could be related to the amount of serum interferon induced by the virus. These results indicate that interferon production may represent one of the factors responsible for the depression of cell-mediated immune reactions during virus infection.The temporary decrease of cell-mediated immune reactions during virus infection is a well-known phenomenon, the mechanism of which has remained largely unexplained. The classic observation in this field was made in 1907 by von Pirquet, who described a decreased reactivity to the tuberculin skin test as a result of infection with measles virus; it has since been repeatedly confirmed and studied in great detail (1). Moreover, depression of tuberculin sensitivity in man also occurs after infection with varicella, influenza, and rubella virus, as well as after vaccination with measles, polio, yellow fever, and mumps virus (2-8). Similar effects have been reported in animals; for example, using skin allograft survival as a measure of cell-mediated immunity, Howard et al. showed that graft survival times were significantly prolonged in mice infected with lactic dehydrogenase virus shortly before or after grafting, and there are many other examples of immunodepression in animals after virus infection (9-11). One common denominator of all virus infections being the production of interferon, we have examined the possibility that interferon is capable of decreasing cell-mediated immune reactions in vivo. There were some good reasons for considering the role of interferon: the prolongation of skin allograft survival described in mice after administration of phytohemagglutinin or concanavalin A, two lectins that are also interferon inducers, and the fact that interferon has been shown to inhibit the proliferative phase of the one-way mixed lymphocyte reaction, which is considered by many to be an in vitro correlate of allograft rejection (12)(13)(14)(15)(16)(17). As a first model of cellmediated immunity, we have studied skin graft rejection in mice across an H-2 barrier, and a small but significant prolongation of graft survival after treatment of recipient mice with either interferon inducers or interferon preparations was observed (18,19). The effect of interferon preparations was independently confirmed by Hirsch et al. (20). In the present study, the effect of interferon on delayed-type hypersensitivity in mice was examined, using two different approaches:(1) interferon induction with Newcastle disease virus (NDV) in high-and low-interferon-producing congenic ...

Inhibition by anti-interferon serum of lymphocytic choriomeningitis virus disease in suckling mice.

“…Thus, the syndrome of decreased growth, liver cell necrosis, and death is only observed in suckling mice treated with interferon or injected with LCM virus; it is not seen in weanling or adult mice. Even in the adult animal it seems likely that some of the common manifestations of virus diseases such as transient immune depression may be due to the interferon (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) induced by the virus rather than to a viral cytolytic effect. It may be that other lesions considered heretofore to be due to cell destruction by the virus may be due in part to host substances (such as interferon) induced by the infectious agent.…”

Electrophoretically pure mouse interferon exerts multiple biologic effects.

“…Expression (34). This experiment was done under conditions comparable to the foregoing, except that the Mr 35,000 interferon fraction was administered 41/2 hr before footpad challenge.…”

“…In addition to interferon's well-known antiviral action, preparations of it have been reported to exert multiple effects on cells [i.e., inhibition of the multiplication of bormal and tumor cells in culture (2)(3)(4)(5), inhibition of the growth of a variety of transplantable tumors in mice (6)(7)(8), modulation of the synthesis and release of specific cellular products (9)(10)(11)(12)(13)(14)(15)(16), modification of the cell surface (17)(18)(19)(20)(21), and modulation of both the humoral (22)(23)(24)(25)(26)(27) and cell-mediated immune responses (28)(29)(30)(31)(32)(33)(34)]. Although experimental results support the hypothesis that the antiviral action of interferon is only one manifestation of its effect on cells (35)(36)(37), it is important to emphasize that these experiments were undertaken using preparations in which interferon protein constituted at most only 1% of the total protein content.…”

Lymphokine Production by PHA-Stimulated Human Lymphocytes is Enhanced by Interferon

“…Specific antibody production by B lymphocytes is either impaired or augment ed depending on the IFN concentration used and the timing of its administration [3,8]. Cell-mediated immune responses, such as delayed-type hypersensitivity reactions, allograft rejection and graft-versus-host re actions have been reported to be suppressed by IFN [5,9,19]. In addition, IFN may in hibit proliferative responses of lymphocytes exposed to polyclonal mitogens and anti gens [2,17].…”