https://www.cell.com/immunity/pdf/S1074-7613(01)00126-1.pdf

Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo.

Publisher Summary This chapter discusses the nature of endotoxins and their interactions with cells of the immune system. The direct interaction of endotoxin with B lymphocytes leading to the formation of antibodies to endotoxin as well as a spectrum of other immunoglobulin molecules is discussed. In addition, the interactions of endotoxins with T cells and macrophages and the associated immunoregulatory effects are discussed. The central role of the lipid A portion of the endotoxin molecule in cellular activation and the molecular events occurring at the cell surface in the course of stimulation are presented. The potential of endotoxins as therapeutic manipulators of the immune response in man is also evaluated. Major direct interactions of endotoxins with B lymphocytes have been documented, leading to synthesis and secretion of antibody directed not only against antigenic determinants on the endotoxin molecules themselves, but also with specificities characteristic of the complete repertoire of variable region gene products. Knowledge of the immunobiology of endotoxins has prompted investigations in their therapeutic uses in man as both antigenically distinct and cross-reactive immunogens in protection against gram-negative infections.

Bacterial endotoxins and host immune responses

Publisher Summary This chapter presents in molecular terms the explanation for immunologic events accompanying lymphocytic choriomeningitis (LCM) infection, including the dual recognition of viral and histocompatibility antigens essential for T cell action and the modulation of viral expression result from the immune response. It discusses the important aspects of nonimmunologic regulation of viral infection particularly the role of defective interfering virus. Lymphocytic choriomeningitis virus (LCMV) and the infection it causes are important subjects of biomedical investigation. First, this virus sporadically causes human illness. The study of LCMV and the disease it causes in its natural murine host has provided the initial findings to open new fields in viral immunobiology, viral immunopathology, and cell–cell recognition. The apparent increased virulence of LCMV on passage through hamsters and the fact that LCMV infection can be transmitted from hamsters to humans suggest important concerns not only for investigators working with LCMV but for experimentalists who use hamsters or hamster tissues in their studies.

The virology and immunobiology of lymphocytic choriomeningitis virus infection.

On the varied biologic effects of interferon

We tested the effect of human leukocyte interferon on early localized herpes zoster infections in three placebo-controlled, randomized double-blind trials involving 90 patients with cancer. There were no significant differences in pretreatment severity of infection or nature of underlying disease in the groups. Higher dosages of more purified interferon in the second and third trials produced a significant (P≤0.01) decrease in cutaneous dissemination. No dissemination occurred in those receiving the highest dosage (5.1 X 105 U per kilogram per day) (P≤0.025). The number of days of new-vesicle formation in the primary dermatome decreased (mean, 2.3 days, P≤0.05) in this group. Treated patients had a trend toward less acute pain, and significantly (P≤0.05) diminished severity of post-herpetic neuralgia, at the two highest dosage levels. Visceral complications were six times less frequent in interferon recipients. High-dosage interferon appeared effective in limiting cutaneous dissemination, viscera...

Human leukocyte Interferon for the treatment of herpes zoster in patients with cancer.

POLYRIBOINOSINIC acid: polyribocytidylic acid [poly (rI)·poly (rC)], endotoxin, polycarboxylate plastics or polysaccharides, and other polyanions induce interferon production (see reviews ref. 1 and 2). They also enhance antibody production3,4, cell-mediated immunity5, and reticuloendothelial activity4,6. It is not yet clear whether or not any of these latter effects are mediated through the action of interferon.

Suppression of mouse antibody producing spleen cells by various interferon preparations.

The effect of repeated stimulation on both the interferon and antibody systems and on reticuloendothelial activity was studied by injection of endotoxin 2 days before injection of (poly rI):(poly rC). A single injection of endotoxin or (poly rI):(poly rC) increased or decreased the response in each system depending on the time of administration. If the injection of (poly rI):(poly rC) was preceded by an injection of endotoxin 2 days before, its activity was markedly reduced in all of the three systems studied. Although different doses of endotoxin were required to induce a state of hyporeactivity or tolerance to the effects of (poly rI):(poly rC) in either system, it is possible that a common mechanism underlies the hyporeactivity in all systems.

Effect of Separate and Combined Injections of Poly rI: Poly rC and Endotoxin on Reticulo-endothelial Activity, Interferon, and Antibody Production in the Mouse.

The release of previously cleared interferon by cycloheximide was studied in the mouse. When cycloheximide was administered after either endogenous interferon stimulation or administration of exogenous interferon, the clearance of interferon from the blood stream was interrupted and a sharp rise in interferon titer occurred approximately 6 hr after cycloheximide administration followed by a rapid decline to low levels. This effect was observed with either interferon stimulated endogenously (by polyriboinosinic·polyribocytidylic acid), or homologous (mouse) or heterologous (rabbit) interferon administered exogenously. Serum protein concentrations also exhibited this rise and fall phenomenon after cycloheximide administration although the magnitude of the change in protein concentrations was less pronounced than that observed with interferon. Hematocrits, although elevated in mice receiving cycloheximide, did not exhibit this rise and fall phenomenon. Hence, cycloheximide administration leads to the release into the circulation of previously cleared interferon as well as other proteins.

https://iai.asm.org/content/iai/5/3/383.full.pdf

Thomas J. Chester

Papers

Suppression of mouse antibody producing spleen cells by various interferon preparations.

Effect of Separate and Combined Injections of Poly rI: Poly rC and Endotoxin on Reticulo-endothelial Activity, Interferon, and Antibody Production in the Mouse.

In vivo release of previously cleared interferon by cycloheximide.